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  • 1.
    de Moraes, Marcia Terezinha Baroni
    et al.
    Oswaldo Cruz Fdn Fiocruz, Brazil; Oswaldo Cruz Fdn Fiocruz, Brazil.
    da Silva, Mauro Franca
    Oswaldo Cruz Fdn Fiocruz, Brazil; Oswaldo Cruz Fdn Fiocruz, Brazil.
    Pimenta, Yan Cardoso
    Oswaldo Cruz Fdn Fiocruz, Brazil; Oswaldo Cruz Fdn Fiocruz, Brazil.
    Cantelli, Carina Pacheco
    Oswaldo Cruz Fdn Fiocruz, Brazil.
    de Assis, Rosane Maria Santos
    Oswaldo Cruz Fdn Fiocruz, Brazil.
    Fialho, Alexandre Madi
    Oswaldo Cruz Fdn Fiocruz, Brazil.
    Bueno, Marina Galvao
    Oswaldo Cruz Fdn Fiocruz, Brazil.
    Olivares, Alberto Ignacio Olivares
    SESAU RR, Brazil; State Univ Roraima, Brazil.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Kalolinska Inst, Sweden.
    Leite, Jose Paulo Gagliardi
    Oswaldo Cruz Fdn Fiocruz, Brazil.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    G6P[8] Rotavirus a Possessing a Wa-like VP3 Gene from a Child with Acute Gastroenteritis Living in the Northwest Amazon Region2023Ingår i: Pathogens, E-ISSN 2076-0817, Vol. 12, nr 7, artikel-id 956Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The introduction of rotavirus A (RVA) vaccines has considerably reduced the RVA-associated mortality among children under 5 years of age worldwide. The ability of RVA to reassort gives rise to different combinations of surface proteins G (glycoprotein, VP7) and P (protease sensitive, VP4) RVA types infecting children. During the epidemiological surveillance of RVA in the Northwest Amazon region, an unusual rotavirus genotype G6P[8] was detected in feces of a 2-year-old child with acute gastroenteritis (AGE) that had been vaccinated with one dose of Rotarix(& REG;) (RV1). The G6P[8] sample had a DS-1-like constellation with a Wa-like VP3 gene mono-reassortment similar to equine-like G3P[8] that has been frequently detected in Brazil previously. The results presented here reinforce the evolutionary dynamics of RVA and the importance of constant molecular surveillance.

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  • 2.
    Hopkins, Francis R.
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Govender, Melissa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svanberg, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Waller, Hjalmar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nilsdotter-Augustinsson, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland. Linköpings universitet, Medicinska fakulteten.
    Henningsson, Anna J.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Division of Clinical Microbiology, Department of Laboratory Medicine in Jönköping, Ryhov County Hospital, Jönköping.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Sjöwall, Johanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland. Linköpings universitet, Medicinska fakulteten.
    Nyström, Sofia N.
    Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Larsson, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-192023Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, artikel-id 1082912Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.

    Methods: Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.

    Results: We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.

    Conclusion: By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.

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  • 3.
    Hellysaz, Arash
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi.
    Neijd, Magdalena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Generó, Magali Marti
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland. Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Microbiota do not restrict rotavirus infection of colon2023Ingår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 97, nr 11, artikel-id e01526-23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rotavirus is associated with extensive infection of the small intestine, whereas colon is considered to be uninfected. Considering that almost all bacteria in the gut colonize the colon, we hypothesized that the microbiota may act as a physical barrier preventing rotavirus infection in the colon in vivo. To address this hypothesis, we used human and mice colonoids, and biopsies of different intestinal segments of untreated and antibiotic-treated adult and infant mice. Rotavirus quantification was performed by qPCR and volumetric 3D imaging of intestinal segments. By 3D imaging, we observed infection in all the small intestinal segments, most extensively in the ileum, with most limited number of infected cells in colon. Broad-spectrum antibiotic treatment yielded no significant change in infection in either ileum or colon of adults and mice pups, although there is a substantial decrease in microbial load. We also show that rotavirus can successfully infect and replicate in colonoids from both mice and humans. Collectively, our data, including novel 3D imaging of the gut, mouse, and human colonoids, conclude that microbiota does not affect rotavirus infection in colon.

    IMPORTANCE

    Alterations of the gut microbiome can have significant effects on gastrointestinal homeostasis leading to various diseases and symptoms. Increased understanding of rotavirus infection in relation to the microbiota can provide better understanding on how microbiota can be used for clinical prevention as well as treatment strategies. Our volumetric 3D imaging data show that antibiotic treatment and its consequent reduction of the microbial load does not alter the extent of rotavirus infection of enterocytes in the small intestine and that restriction factors other than bacteria limit the infection of colonocytes.

  • 4.
    Reyes, Yaoska
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Natl Autonomous Univ Nicaragua Leon, Nicaragua; Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    St Jean, Denise T.
    Univ N Carolina, NC USA.
    Bowman, Natalie M.
    Univ N Carolina, NC USA.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Mijatovic-Rustempasic, Slavica
    CDCP, GA USA.
    Becker-Dreps, Sylvia
    Univ N Carolina, NC USA; Univ N Carolina, NC USA.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Bucardo, Filemon
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Vielot, Nadja A.
    Univ N Carolina, NC USA.
    Nonsecretor Phenotype Is Associated With Less Risk of Rotavirus-Associated Acute Gastroenteritis in a Vaccinated Nicaraguan Birth Cohort2023Ingår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 228, nr 12, s. 1739-1747Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations. Methods Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by reverse-transcription quantitative polymerase chain reaction, and saliva or blood was used to determine HBGA phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. Results Rotavirus was detected in 109 (7%) stool samples from 1689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11 [24%]) and equine-like G3P[8] (11 [24%]). The overall incidence of rotavirus-associated AGE was 9.2 per 100 child-years, and was significantly higher in secretor than nonsecretor children (9.8 vs 3.5/100 child-years, P = .002). Conclusions The nonsecretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children. Overall incidence of rotavirus-associated AGE in a vaccinated Nicaraguan birth cohort was 9.2/100 child-years. Nonsecretor children had less risk of symptomatic rotavirus infection. These results are important in the context of monitoring effectiveness of rotavirus vaccine trough birth cohort studies.

  • 5.
    Hopkins, Francis
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Fernandez-Botran, Rafael
    Univ Louisville, KY USA.
    Enocsson, Helena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Govender, Melissa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svanberg, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nilsdotter-Augustinsson, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Nyström, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sjöwall, Johanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Larsson, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Pentameric C-reactive protein is a better prognostic biomarker and remains elevated for longer than monomeric CRP in hospitalized patients with COVID-192023Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, artikel-id 1259005Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The differing roles of the pentameric (p) and monomeric (m) C-reactive protein (CRP) isoforms in viral diseases are not fully understood, which was apparent during the COVID-19 pandemic regarding the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we investigated the predictive value of the pCRP and mCRP isoforms for COVID-19 severity in hospitalized patients and evaluated how the levels of the protein isoforms changed over time during and after acute illness. This study utilized samples from a well-characterized cohort of Swedish patients with SARS-CoV-2 infection, the majority of whom had known risk factors for severe COVID-19 and required hospitalization. The levels of pCRP were significantly raised in patients with severe COVID-19 and in contrast to mCRP the levels were significantly associated with disease severity. Additionally, the pCRP levels remained elevated for at least six weeks post inclusion, which was longer compared to the two weeks for mCRP. Our data indicates a low level of inflammation lasting for at least six weeks following COVID-19, which might indicate that the disease has an adverse effect on the immune system even after the viral infection is resolved. It is also clear that the current standard method of testing pCRP levels upon hospitalization is a useful marker for predicting disease severity and mCRP testing would not add any clinical relevance for patients with COVID-19.

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  • 6.
    Waller, Hjalmar
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Carmona Vicente, Noelia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    James, Axel
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Govender, Melissa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Hopkins, Francis
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Larsson, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Enocsson, Helena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Gustafsson, Annette
    Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Nilsdotter-Augustinsson, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Sjöwall, Johanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland. Vrinnevi Hosp, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Viral load at hospitalization is an independent predictor of severe COVID-192023Ingår i: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 53, nr 1, artikel-id e13882Artikel i tidskrift (Refereegranskat)
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  • 7.
    Vielot, Nadja Alexandra
    et al.
    Univ N Carolina, NC 27515 USA.
    Francois, Ruthly
    Univ N Carolina, NC 27515 USA.
    Huseynova, Emilya
    Univ N Carolina, NC 27515 USA.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Reyes, Yaoska
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Gutierrez, Lester
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Toval-Ruiz, Christian
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Vilchez, Samuel
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Vinje, Jan
    Ctr Dis Control & Prevent, GA USA.
    Becker-Dreps, Sylvia
    Univ N Carolina, NC 27515 USA; Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Bucardo, Filemon
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Association between breastfeeding, host genetic factors, and calicivirus gastroenteritis in a Nicaraguan birth cohort2022Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 17, nr 10, artikel-id e0267689Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Norovirus and sapovirus are important causes of childhood acute gastroenteritis (AGE). Breastfeeding prevents AGE generally; however, it is unknown if breastfeeding prevents AGE caused specifically by norovirus and sapovirus. Methods We investigated the association between breastfeeding and norovirus or sapovirus AGE episodes in a birth cohort. Weekly data on breastfeeding and AGE episodes were captured during the first year of life. Stools were collected from children with AGE and tested by RT-qPCR for norovirus and sapovirus. Time-dependent Cox models estimated associations between weekly breastfeeding and time to first norovirus or sapovirus AGE. Findings From June 2017 to July 2018, 444 newborns were enrolled in the study. In the first year of life, 69 and 34 children experienced a norovirus and a sapovirus episode, respectively. Exclusive breastfeeding lasted a median of 2 weeks, and any breastfeeding lasted a median of 43 weeks. Breastfeeding in the last week did not prevent norovirus (HR: 1.09, 95% CI: 0.62, 1.92) or sapovirus (HR: 1.00, 95% CI: 0.82, 1.21) AGE in a given week, adjusting for household sanitation, consumption of high-risk foods, and mothers and childs histo-blood group phenotypes. Maternal secretor-positive phenotype was protective against norovirus AGE, whereas childs secretor-positive phenotype was a risk factor for norovirus AGE. Interpretation Exclusive breastfeeding in this population was short-lived, and no conclusions could be drawn about its potential to prevent norovirus or sapovirus AGE. Non-exclusive breastfeeding did not prevent norovirus or sapovirus AGE in the first year of life. However, maternal secretor-positive phenotype was associated with a reduced hazard of norovirus AGE.

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  • 8.
    Hagbom, Marie
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Carmona Vicente, Noelia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Olsson, Henrik
    Noviral Sweden AB, Sweden.
    Jämtberg, Mikael
    Noviral Sweden AB, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Sjöwall, Johanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Evaluation of SARS-CoV-2 rapid antigen diagnostic tests for saliva samples2022Ingår i: Heliyon, E-ISSN 2405-8440, Vol. 8, nr 2, artikel-id e08998Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using saliva samples would facilitate sample collection, diagnostic feasibility, and mass screening of SARS-CoV-2. We tested two rapid antigen (RAD) immunochromatographic tests designed for detection of SARS-CoV-2 in saliva: Rapid Response (TM) COVID-19 Antigen Rapid Test Cassette for oral fluids and DIAGNOS (TM) COVID-19 Antigen Saliva Test. Evaluation of detection limit was performed with purified SARS-CoV-2 nucleocapsid protein and live SARSCoV-2 virus. Sensitivity and specificity were further evaluated with reverse transcription quantitative PCR (RTqPCR) positive and negative saliva samples from hospitalized individuals with COVID-19 (n = 39) and healthcare workers (n = 20). DIAGNOS showed higher sensitivity than Rapid Response for both nucleocapsid protein and live virus. The limit of detection of the saliva test from DIAGNOS was further comparable with the Abbott Panbio (TM) COVID-19 Ag Rapid Test designed for nasopharyngeal samples. DIAGNOS and Rapid Response detected nine (50.0%) and seven (38.9%), respectively, of the 18 RT-qPCR positive saliva samples. All RT-qPCR negative saliva (n = 41) were negative with both tests. Only one of the RT-qPCR positive saliva samples contained infectious virus as determined by cell culture and was also positive using the saliva RADs. The results show that the DIAGNOS may be an important and easy-to-use saliva RAD complement to detect SARS-CoV-2 positive individuals, but validation with a larger sample set is warranted.

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  • 9.
    Ottosson, Loa
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svernlöv, Rikard
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Mag- tarmmedicinska kliniken.
    Nyström, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Carlsson, Beatrice
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Öman, Mattias
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Ström, Magnus
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Mag- tarmmedicinska kliniken.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Division of Infectious Diseases, Department of Medicine, Karolinska Institute, 17111 Stockholm, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Long Term Norovirus Infection in a Patient with Severe Common Variable Immunodeficiency2022Ingår i: Viruses, E-ISSN 1999-4915, Vol. 14, nr 8, artikel-id 1708Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Norovirus is the most common cause of acute non-bacterial gastroenteritis. Immunocompromised patients can become chronically infected, with or without symptoms. In Europe, common variable immunodeficiency (CVID) is one of the most common inborn errors of immunity. A potentially severe complication is CVID-associated enteropathy, a disorder with similar histopathology to celiac disease. Studies suggest that chronic norovirus infection may be a contributor to CVID enteropathy, and that the antiviral drug ribavirin can be effective against norovirus. Here, a patient with CVID-like disease with combined B- and T-cell deficiency, had chronic norovirus infection and enteropathy. The patient was routinely administered subcutaneous and intravenous immunoglobulin replacement therapy (SCIg and IVIg). The patient was also administered ribavirin for -7.5 months to clear the infection. Stool samples (collected 2013-2016) and archived paraffin embedded duodenal biopsies were screened for norovirus by qPCR, confirming a chronic infection. Norovirus genotyping was done in 25 stool samples. For evolutionary analysis, the capsid (VP1) and polymerase (RdRp) genes were sequenced in 10 and 12 stool samples, respectively, collected before, during, and after ribavirin treatment. Secretor phenotyping was done in saliva, and serum was analyzed for histoblood group antigen (HBGA) blocking titers. The chronic norovirus strain formed a unique variant subcluster, with GII.4 Den Haag [P4] variant, circulating around 2009, as the most recent common ancestor. This corresponded to the documented debut of symptoms. The patient was a secretor and had HBGA blocking titers associated with protection in immunocompetent individuals. Several unique amino acid substitutions were detected in immunodominant epitopes of VP1. However, HBGA binding sites were conserved. Ribavirin failed in treating the infection and no clear association between ribavirin-levels and quantity of norovirus shedding was observed. In conclusion, long term infection with norovirus in a patient with severe CVID led to the evolution of a unique norovirus strain with amino acid substitutions in immunodominant epitopes, but conservation within HBGA binding pockets. Regularly administered SCIg, IVIg, and similar to 7.5-month ribavirin treatment failed to clear the infection.

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  • 10.
    Sjöwall, Johanna
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Hjorth, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Gustafsson, Annette
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Göransson, Robin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Larsson, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Waller, Hjalmar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nilsdotter-Augustinsson, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Nyström, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    SARS-CoV-2 Specific Antibody Response and T Cell-Immunity in Immunocompromised Patients up to Six Months Post COVID: A Pilot Study2022Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 11, nr 12, artikel-id 3535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    COVID-19 generates SARS-CoV-2-specific antibodies in immunocompetent individuals. However, in immunocompromised patients, the humoral immunity following infection may be impaired or absent. Recently, the assessment of cellular immunity to SARS-CoV-2, both following natural infection and vaccination, has contributed new knowledge regarding patients with low or no antibody responses. As part of a prospective cohort study which included hospitalized patients with COVID-19, we identified immunocompromised patients and compared them with age- and sex-matched immunocompetent patients regarding co-morbidities, biomarkers of COVID-19 and baseline viral load by real-time PCR in nasopharyngeal swabs. Spike and nucleocapsid antibody responses were analyzed at inclusion and after two weeks, six weeks and six months. Plasma immunoglobulin G (IgG) levels were quantified, lymphocyte phenotyping was performed, and SARS-CoV-2 specific CD4 and CD8 T cell responses after in vitro antigen stimulation were assessed at six months post infection. All patients showed IgG levels above or within reference limits. At six months, all patients had detectable SARS-CoV-2 anti-spike antibody levels. SARS-CoV-2 specific T cell responses were detected in 12 of 12 immunocompetent patients and in four of six immunocompromised patients. The magnitude of long-lived SARS-CoV-2 specific T cell responses were significantly correlated with the number of CD4 T cells and NK cells. Determining the durability of the humoral and cellular immune response against SARS-CoV-2 in immunocompromised individuals could be of importance by providing insights into the risk of re-infection and the need for vaccine boosters.

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  • 11.
    Reyes, Yaoska
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Gutierrez, Lester
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Blandon, Patricia
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Centeno, Edwing
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Zepeda, Omar
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Toval-Ruiz, Christian
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Lindesmith, Lisa C.
    Univ N Carolina, NC 27515 USA.
    Baric, Ralph S.
    Univ N Carolina, NC 27515 USA.
    Vielot, Nadja
    Univ N Carolina, NC 27515 USA.
    Diez-Valcarce, Marta
    Ctr Dis Control & Prevent, GA USA; Emory Univ, GA 30322 USA.
    Vinje, Jan
    Ctr Dis Control & Prevent, GA USA.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Becker-Dreps, Sylvia
    Univ N Carolina, NC 27515 USA; Univ N Carolina, NC 27515 USA.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Bucardo, Filemon
    Natl Autonomous Univ Nicaragua Leon, Nicaragua.
    Secretor Status Strongly Influences the Incidence of Symptomatic Norovirus Infection in a Genotype-Dependent Manner in a Nicaraguan Birth Cohort2022Ingår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 225, nr 1, s. 105-115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. Methods. Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and histo-blood group antigens (HBGAs) were determined by phenotyping of saliva and blood. Hazard ratios and predictors of norovirus acute gastroenteritis (AGE) outcome stratified by HBGA were estimated using Cox proportional hazards models. Results. Of 1353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months of age and had a higher incidence of norovirus GII compared to nonsecretor children (15.4 vs 4.1/100 child-years, P = .006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted odds ratio [aOR], 0.09 [95% confidence interval {CI}, .02-.33]) or non-GII.4 viruses (aOR, 0.2 [95% CI, .07-.6]) were less likely to have severe AGE compared to GII.4-infected children. Conclusions. Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.

  • 12.
    Swartling, Lisa
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Sparrelid, Elda
    Karolinska Inst, Sweden.
    Ljungman, Per
    Karolinska Univ Hosp Huddinge, Sweden; Karolinska Inst, Sweden.
    Boriskina, Ksenia
    Karolinska Univ Hosp Huddinge, Sweden.
    Valentini, Davide
    Karolinska Univ Hosp Huddinge, Sweden.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    The Importance of Secretor-Status in Norovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation2022Ingår i: Viruses, E-ISSN 1999-4915, Vol. 14, nr 7, artikel-id 1350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Human secretor-status is a strong susceptibility factor for norovirus infection in immunocompetent people. The predominant norovirus genotype GII.4 almost exclusively infects secretors and is also associated with more severe symptoms. However, it is not known to what extent this also applies to immunocompromised individuals. Our objective was to determine the importance of secretor-status and norovirus genotype for the susceptibility and/or the clinical course of norovirus infection in allogeneic hematopoietic stem cell transplant (HCT) patients. Methods: This was a retrospective study of 89 HCT patients diagnosed with norovirus infection. Secretor-status and norovirus genotype were determined using stored extracted DNA or blood (n = 89) and fecal samples (n = 22), respectively. Results: Seven of eighty-nine (8%) of the patients were secretor-negative, a small proportion compared to the expected rate of at least 20% non-secretors in the general Swedish population. Among the genotyped samples, norovirus genotype GII.4 was predominant (n = 12) and only detected in secretor-positive individuals. Patients with norovirus GII.4 had a median symptom duration of 36 (3-681) days compared to 15 (1-94) days in patients infected with other norovirus genotypes (n = 10, p = 0.1). Conclusions: The results suggest that secretor-status affects the susceptibility to norovirus infection even when the immune system is severely compromised. The norovirus genotype may also be a risk factor for chronic norovirus symptoms in immunocompromised patients.

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  • 13.
    Bucardo, Filemon
    et al.
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Reyes, Yaoska
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Morales, Marlen
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Briceno, Rafaela
    Minist Hlth Leon, Nicaragua.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Lundkvist, Ake
    Uppsala Univ, Sweden.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor a Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua2021Ingår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 223, nr 2, s. 278-286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) alpha, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya. Methods. To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in Leon, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays. Results. After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-alpha with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively). Conclusion. This study identified polymorphisms in DC-SIGN, TLR3, and TNF-alpha genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.

  • 14.
    Sharma, Sumit
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Effect of Infant and Maternal Secretor Status on Rotavirus Vaccine Take-An Overview2021Ingår i: Viruses, E-ISSN 1999-4915, Vol. 13, nr 6, artikel-id 1144Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of alpha-1,2 fucosylated blood group antigens in mucosa and secretions, yielding the secretor-positive phenotype. Secretors are more susceptible to infection with predominant rotavirus genotypes, as well as to the commonly used live rotavirus vaccines. Difference in susceptibility to the vaccines is one proposed factor for the varying degree of efficacy observed between countries. Besides infection susceptibility, secretor status has been found to modulate rotavirus specific antibody levels in adults, as well as composition of breastmilk in mothers and microbiota of the infant, which are other proposed factors affecting rotavirus vaccine take. Here, the known and possible effects of secretor status in both infant and mother on rotavirus vaccine take are reviewed and discussed.

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  • 15.
    Olivares, Alberto Ignacio Olivares
    et al.
    Fiocruz MS, Brazil; Fiocruz MS, Brazil.
    Leitao, Gabriel Azevedo Alves
    Fiocruz MS, Brazil; Fiocruz MS, Brazil.
    Pimenta, Yan Cardoso
    Fiocruz MS, Brazil; Fiocruz MS, Brazil.
    Cantelli, Carina Pacheco
    Fiocruz MS, Brazil.
    Fumian, Tulio Machado
    Fiocruz MS, Brazil.
    Fialho, Alexandre Madi
    Fiocruz MS, Brazil.
    da Silva e Mouta Junior, Sergio
    Fiocruz MS, Brazil.
    Delgado, Isabella Fernandes
    Fiocruz MS, Brazil.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Miagostovich, Marize Pereira
    Fiocruz MS, Brazil.
    Leite, Jose Paulo Gagliardi
    Fiocruz MS, Brazil.
    Moraes, Marcia Terezinha Baroni de
    Fiocruz MS, Brazil.
    Epidemiology of enteric virus infections in children living in the Amazon region2021Ingår i: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 108, s. 494-502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To verify the frequency of viruses causing acute gastroenteritis (AGE) in association with the histo-blood group antigen (HBGA) and Rotarix (TM) vaccination coverage in children from the Amazon region. Design: Fecal and saliva samples were collected from children with AGE (n = 485) and acute respiratory infection (ARI) (n = 249) clinical symptoms. Rotavirus A (RVA), norovirus, human adenovirus (HAdV), and sapovirus (SaV) were verified in feces by molecular detection. Saliva samples were used for HBGA phenotyping/FUT3 genotyping. Blood group types, clinical aspects and Rotarix (TM) RVA vaccination data were recorded. Results: Norovirus remained the most prevalently detected cause of AGE (38%, 184/485 and ARI 21.3%, 53/249). High HAdV frequencies were observed in AGE children (28.6%, 139/485) and ARI children (37.3%, 93/249). RVA was the third most prevalent virus causing AGE (22.7%, 110/485 and ARI 19.3%, 48/249) and a low RV1 coverage (61%, 448/734) was verified. The SaV frequencies were lower (7.2%, 35/485 for AGE and 6.8%, 17/249 for ARI). Secretor children were HBGA susceptible to HAdV infection (OR 1.5, 95% CI 1.0-2.3; P = 0.04) but not to RVA, norovirus or SaV infection. Conclusions: Norovirus could be considered the main etiological agent of AGE. No association was verified for HBGA susceptibility to RVA, norovirus and SaV. Secretor children showed a slight susceptibility to HAdV infection and the Le (a-b-) heterogeneous SNPs on the FUT3 gene. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

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  • 16.
    Sharma, Sumit
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi.
    Hagbom, Marie
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi.
    Svensson, Lennart
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland. Karolinska Institute, Stockholm, Sweden.
    Nordgren, Johan
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi.
    Human Norovirus and Sapovirus2021Ingår i: Encyclopedia of Virology: Fourth Edition / [ed] Dennis H. Bamford; Mark Zuckerman, Academic Press, 2021, 2, s. 483-492Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    The Caliciviridae family includes human norovirus and sapovirus. These are a diverse set of viruses causing acute gastroenteritis (AGE) in people of all ages, with norovirus being responsible for approximately 20% of all AGE worldwide and sapovirus 3%–17% of AGE in children, respectively. Susceptibility to norovirus is associated with human genetics, with approximately one-fifth of the population being resistant to the predominant GII.4 genotype. A human enteroid model has recently been successfully established to address questions regarding pathogenesis and virus–host interactions. While no specific antivirals are available, norovirus vaccine candidates are in clinical trials.

  • 17.
    de Moraes, Marcia Terezinha Baroni
    et al.
    Fundacao Oswaldo Cruz, Brazil.
    Leitao, Gabriel Azevedo Alves
    Fundacao Oswaldo Cruz, Brazil.
    Olivares, Alberto Ignacio Olivares
    SESAU RR, Brazil.
    Xavier, Maria da Penha Trindade Pinheiro
    Fundacao Oswaldo Cruz, Brazil.
    Bispo, Romanul de Souza
    Univ Fed Roraima, Brazil.
    Sharma, Sumit
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Leite, Jose Paulo Gagliardi
    Fundacao Oswaldo Cruz, Brazil.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Molecular Epidemiology of Sapovirus in Children Living in the Northwest Amazon Region2021Ingår i: Pathogens, E-ISSN 2076-0817, Vol. 10, nr 8, artikel-id 965Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sapovirus is an important etiological agent of acute gastroenteritis (AGE), mainly in children under 5 years old living in lower-income communities. Eighteen identified sapovirus genotypes have been observed to infect humans. The aim of this study was to identify sapovirus genotypes circulating in the Amazon region. Twenty-eight samples were successfully genotyped using partial sequencing of the capsid gene. The genotypes identified were GI.1 (n = 3), GI.2 (n = 7), GII.1 (n = 1), GII.2 (n = 1), GII.3 (n = 5), GII.5 (n = 1), and GIV.1 (n = 10). The GIV genotype was the most detected genotype (35.7%, 10/28). The phylogenetic analysis identified sapovirus genotypes that had no similarity with other strains reported from Brazil, indicating that these genotypes may have entered the Amazon region via intense tourism in the Amazon rainforest. No association between histo-blood group antigen expression and sapovirus infection was observed.

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  • 18.
    Hagbom, Marie
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Lin, Jenny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Falkeborn, Tina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi.
    Serrander, Lena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi.
    Albert, Jan
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Replication in Human Intestinal Enteroids of Infectious Norovirus from Vomit Samples2021Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 27, nr 8, s. 2212-2214Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A typical clinical symptom of human norovirus infection is projectile vomiting. Although norovirus RNA and viral particles have been detected in vomitus, infectivity has not yet been reported. We detected replication-competent norovirus in 25% of vomit samples with a 13-fold to 714-fold increase in genomic equivalents, confirming infectious norovirus.

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  • 19.
    Nordgren, Johan
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Olsson, Henrik
    Noviral Sweden AB, Sweden.
    Jamtberg, Mikael
    Noviral Sweden AB, Sweden.
    Falkeborn, Tina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    SARS-CoV-2 rapid antigen test: High sensitivity to detect infectious virus2021Ingår i: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 140, artikel-id 104846Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The COVID-19 pandemic has highlighted the need for rapid, cost effective and easy-to-use diagnostic tools for SARS-CoV-2 infections that can be used in point of care settings to limit disease transmission. Objective: We evaluated two rapid antigen immunochromatographic tests, Abbott PanbioTM COVID-19 Ag Rapid Test (Panbio) and Zhejiang Orient Gene/Healgen Biotech Coronavirus Ag rapid test cassette (Orient gene) for detection of infectious SARS-CoV-2. Results: The tests were evaluated on nasopharyngeal samples taken from individuals having respiratory and/or COVID-19 related symptoms, which had been analyzed for SARS-CoV-2 RNA using real-time PCR. In total 156 PCR-positive, and 130 (Panbio) and 176 (Orient Gene) PCR-negative samples were analyzed. Overall sensitivity and specificity were 71.8% and 100% for Panbio and 79.5% and 74.4% for the Orient Gene test respectively. The false positives by the Orient Gene test were verified as SARS-CoV-2 negative by in-house real-time PCR assay and were negative for the four seasonal coronaviruses. Subgroup analysis revealed that the antigen tests had high sensitivity for samples with Ct-values <25 (>88%) and for samples containing infectious viruses as determined by cultivation on Vero cells, 94.1% and 97.1% for the Panbio and Orient gene tests, respectively. Furthermore, both tests had a sensitivity of <50 picogram for nucleocapsid protein. No sample with a Ct-value >27 was shown to contain infectious virus. Conclusion: The results indicate that the rapid antigen tests, especially the Panbio tests may be a valuable tool to detect contagious persons during the ongoing pandemic.

  • 20.
    Hagbom, Marie
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Hellysaz, Arash
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Istrate, Claudia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Univ Lisbon, Portugal.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Meira de Faria, Felipe
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    The 5-HT3 Receptor Affects Rotavirus-Induced Motility2021Ingår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 95, nr 15, artikel-id e00751-21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rotavirus infection is highly prevalent in children, and the most severe effects are diarrhea and vomiting. It is well accepted that the enteric nervous system (ENS) is acti-vated and plays an important role, but knowledge of how rotavirus activates nerves within ENS and to the vomiting center is lacking. Serotonin is released during rotavirus infection, and antagonists to the serotonin receptor subtype 3 (5-HT3 receptor) can attenuate rotavi-rus-induced diarrhea. In this study, we used a 5-HT3 receptor knockout (KO) mouse model to investigate the role of this receptor in rotavirus-induced diarrhea, motility, electrolyte secretion, inflammatory response, and vomiting reflex. The number of diarrhea days (P= 0.03) and the number of mice with diarrhea were lower in infected 5-HT3 receptor KO than wild-type pups. In vivo investigation of fluorescein isothiocyanate (FITC)-dextran transit time showed that intestinal motility was lower in the infected 5-HT3 receptor KO compared to wild-type mice (P= 0.0023). Ex vivo Ussing chamber measurements of poten-tial difference across the intestinal epithelia showed no significant difference in electrolyte secretion between the two groups. Immediate early gene cFos expression level showed no difference in activation of the vomiting center in the brain. Cytokine analysis of the intestine indicated a low effect of inflammatory response in rotavirus-infected mice lack -ing the 5-HT3 receptor. Our findings indicate that the 5-HT3 receptor is involved in rotavi-rus-induced diarrhea via its effect on intestinal motility and that the vagus nerve signaling to the vomiting center occurs also in the absence of the 5-HT3 receptor. IMPORTANCE The mechanisms underlying rotavirus-induced diarrhea and vomiting are not yet fully understood. To better understand rotavirus pathophysiology, characterization of nerve signaling within the ENS and through vagal efferent nerves to the brain, which have been shown to be of great importance to the disease, is necessary. Serotonin (5-HT), a mediator of both diarrhea and vomiting, has been shown to be released from entero-chromaffin cells in response to rotavirus infection and the rotavirus enterotoxin NSP4. Here, we investigated the role of the serotonin receptor 5-HT3, which is known to be involved in the nerve signals that regulate gut motility, intestinal secretion, and signal transduction through the vagus nerve to the brain. We show that the 5-HT3 receptor is involved in rotavirus-induced diarrhea by promoting intestinal motility. The findings shed light on new treatment possibilities for rotavirus diarrhea.

  • 21.
    Hagbom, Marie
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Meira de Faria, Felipe
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Tinnerfelt Winberg, Martin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Westerberg, Sonja
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Keita, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Loitto, Vesa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Neurotrophic Factors Protect the Intestinal Barrier from Rotavirus Insult in Mice2020Ingår i: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 11, nr 1, artikel-id e02834-19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Increased intestinal permeability has been proposed as a mechanism of rotavirus-induced diarrhea. Studies with humans and mice have, however, shown that rotavirus leaves intestinal permeability unaffected or even reduced during diarrhea, in contrast to most bacterial infections. Gastrointestinal permeability is regulated by the vagus nerve and the enteric nervous system, which is composed of neurons and enteric glial cells (EGCs). We investigated whether the vagus nerve, serotonin (5-HT), EGCs, and neurotropic factors contribute to maintaining gut barrier homeostasis during rotavirus infection. Using subdiaphragmatic vagotomized and 5-HT3 receptor knockout mice, we found that the unaffected epithelial barrier during rotavirus infection is independent of the vagus nerve but dependent on 5-HT signaling through enteric intrinsic 5-HT3 receptors. Immunofluorescence analysis showed that rotavirus-infected enterocytes were in close contact with EGCs and enteric neurons and that the glial cell-derived neurotrophic factor (GDNF) was strongly upregulated in enterocytes of infected mice. Moreover, rotavirus and 5-HT activated EGCs (P < 0.001). Using Ussing chambers, we found that GDNF and S-nitrosoglutathione (GSNO) led to denser epithelial barriers in small intestinal resections from noninfected mice (P < 0.01) and humans (P < 0.001) and that permeability was unaffected in rotavirus-infected mice. GSNO made the epithelial barrier denser in Caco-2 cells by increasing the expression of the tight junction protein zona occludens 1 (P < 0.001), resulting in reduced passage of fluorescein isothiocyanate dextran (P < 0.05) in rotavirus-infected monolayers. This is the first report to show that neurotropic factors contribute to maintaining the gut epithelial barrier during viral insult. IMPORTANCE Human and mouse studies have shown that rotavirus infection is associated with low inflammation and unaffected intestinal barrier at the time of diarrhea, properties different from most bacterial and inflammatory diseases of the gut. We showed by in vitro, ex vivo, and in vivo experiments that neurotrophic factors and 5-HT have barrier protective properties during rotavirus insult. These observations advance our understanding of how the gut barrier is protected against rotavirus and suggest that rotavirus affects the gut barrier differently from bacteria. This is the first report to show that neurotrophic factors contribute to maintain the gut epithelial barrier during viral insult.

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  • 22.
    Rönnelid, Ylva
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Bonkoungou, I. J. O.
    Univ Joseph KI ZERBO, Burkina Faso.
    Ouedraogo, N.
    Univ Dedougou, Burkina Faso.
    Barro, N.
    Univ Joseph KI ZERBO, Burkina Faso.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Norovirus and rotavirus in children hospitalised with diarrhoea after rotavirus vaccine introduction in Burkina Faso2020Ingår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 148, artikel-id e245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies report norovirus as the new leading cause of severe gastroenteritis in children after the global introduction of rotavirus vaccines. Burkina Faso introduced general rotavirus vaccination with the oral pentavalent vaccine RotaTeq in November 2013 and quickly reached a vaccine coverage of >90%. This study describes detection rates, clinical profiles and the molecular epidemiology of norovirus and rotavirus infections in 146 children aged <5 years with severe acute gastroenteritis in Ouagadougou, consecutively enrolled from a hospital between January 2015 and December 2015. Virus detection was performed with an antigen test or real-time polymerase chain reaction (PCR) and genotyping was performed by nucleotide sequencing or multiplex PCR. Rotavirus was found in 14% and norovirus in 20% of faecal samples. Norovirus infection was significantly more associated with severe dehydration compared to rotavirus (P < 0.001). Among genotyped norovirus samples 48% (12/25) belonged to GII.4 which caused significantly more diarrhoeal episodes than non-GII.4 genotypes (P = 0.01). The most common rotavirus genotypes were G2P[4] (30%), G12P[6] (25%) and G12P[8] (20%). Fifty percent of the rotavirus positive children were infected with fully or partly heterotypic strains. In conclusion, this study found a higher proportion of norovirus causing more severe symptoms in children with diarrhoea in Burkina Faso after the introduction of rotavirus vaccination.

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  • 23.
    Cantelli, Carina Pacheco
    et al.
    Fiocruz MS, Brazil.
    Fumian, Tulio Machado
    Fiocruz MS, Brazil.
    Malta, Fabio Correia
    Fiocruz MS, Brazil.
    da Cunha, Denise Cotrim
    Fiocruz MS, Brazil.
    Brasil, Patricia
    Fiocruz MS, Brazil.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Miagostovich, Marize Pereira
    Fiocruz MS, Brazil.
    Baroni de Moraes, Marcia Terezinha
    Fiocruz MS, Brazil.
    Gagliardi Leite, Jose Paulo
    Fiocruz MS, Brazil.
    Norovirus infection and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil2020Ingår i: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 82, artikel-id 104280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Norovirus has emerged as an important viral agent of acute pediatric gastroenteritis, with a growing genetic diversity reported in the last decades. Histo-blood group antigens (HBGAs) present on the surface of enterocytes are susceptibility factors for norovirus infection and differ between populations which could affects the epidemiology and evolution of these viruses. This study investigated the frequency, incidence and genetic diversity of noroviruses in a cohort of rotavirus A vaccinated children in association to the host HBGA (Secretor/Lewis) genetic susceptibility profile. Norovirus genogroups I and II (GI/GII) were screened by RT-qPCR in 569 stool samples from 132 children followed-up from birth to 11 months of age during 2014-2018. Noroviruses were identified in 21.2% of children enrolled in this study, with a norovirus detection rate of 5.6% (32/569), in 17.1% and 4.7% of acute diarrheic episodes (ADE) and non-ADE, respectively. The norovirus incidence was 5.8 infections per 100 child-months. Partial nucleotide sequencing characterized six different norovirus genotypes, with GII.4 Sydney 2012 being detected in 50% associated with three different polymerase genotypes (GII.31, GII.P16 and GII.P4 New Orleans 2009). FUT3 genotyping was yielded seven new mutations in this population. A significant association between symptomatic norovirus infection and secretor profile could be inferred.

  • 24.
    Cantelli, Carina Pacheco
    et al.
    Fiocruz MS, Brazil; Fiocruz MS, Brazil.
    Velloso, Alvaro Jorge
    Fiocruz MS, Brazil.
    Santos de Assis, Rosane Maria
    Fiocruz MS, Brazil.
    Barros, Jose Junior
    Fiocruz MS, Brazil.
    do Amaral Mello, Francisco Campello
    Fiocruz MS, Brazil.
    da Cunha, Denise Cotrim
    Fiocruz MS, Brazil.
    Brasil, Patricia
    Fiocruz MS, Brazil.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Miagostovich, Marize Pereira
    Fiocruz MS, Brazil.
    Gagliardi Leite, Jose Paulo
    Fiocruz MS, Brazil.
    de Moraes, Marcia Terezinha Baroni
    Fiocruz MS, Brazil.
    Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014-20182020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 6965Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1(st)/2(nd) RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a-b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.

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  • 25.
    Sharma, Sumit
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Carlsson, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Nederby Ohd, Johanna
    Stockholm Cty Council, Sweden; Karolinska Inst, Sweden.
    Insulander, Mona
    Stockholm Cty Council, Sweden.
    Eriksson, Ronnie
    Natl Food Agcy, Sweden.
    Simonsson, Magnus
    Natl Food Agcy, Sweden.
    Widerstrom, Micael
    Stockholm Cty Council, Sweden; Umea Univ, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Secretor Status is Associated with Susceptibility to Disease in a Large GII.6 Norovirus Foodborne Outbreak2020Ingår i: Food and Environmnetal Virology, ISSN 1867-0334, E-ISSN 1867-0342, Vol. 12, s. 28-34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Norovirus is commonly associated with food and waterborne outbreaks. Genetic susceptibility to norovirus is largely dependent on presence of histo-blood group antigens (HBGA), specifically ABO, secretor, and Lewis phenotypes. The aim of the study was to determine the association between HBGAs to norovirus susceptibility during a large norovirus foodborne outbreak linked to genotype GII.6 in an office-based company in Stockholm, Sweden, 2015. A two-episode outbreak with symptoms of diarrhea and vomiting occurred in 2015. An online questionnaire was sent to all 1109 employees that had worked during the first outbreak episode. Food and water samples were collected from in-house restaurant and tested for bacterial and viral pathogens. In addition, fecal samples were collected from 8 employees that had diarrhea. To investigate genetic susceptibility during the outbreak, 98 saliva samples were analyzed for ABO, secretor, and Lewis phenotypes using ELISA. A total of 542 of 1109 (49%) employees reported gastrointestinal symptoms. All 8 fecal samples tested positive for GII norovirus, which was also detected in coleslaw collected from the in-house restaurant. Eating at the in-house restaurant was significantly associated with risk of symptom development. Nucleotide sequencing was successful for 5/8 fecal samples and all belonged to the GII.6 genotype. HBGA characterization showed a strong secretor association to norovirus-related symptoms (P = 0.014). No association between norovirus disease and ABO phenotypes was observed. The result of this study shows that non-secretors were significantly less likely to report symptoms in a large foodborne outbreak linked to the emerging GII.6 norovirus strain.

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  • 26.
    Sharma, Sumit
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Hagbom, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    The Impact of Human Genetic Polymorphisms on Rotavirus Susceptibility, Epidemiology, and Vaccine Take2020Ingår i: VIRUSES-BASEL, Vol. 12, nr 3, artikel-id 324Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Innate resistance to viral infections can be attributed to mutations in genes involved in the immune response, or to the receptor/ligand. A remarkable example of the latter is the recently described Mendelian trait resistance to clinically important and globally predominating genotypes of rotavirus, the most common agent of severe dehydrating gastroenteritis in children worldwide. This resistance appears to be rotavirus genotype-dependent and is mainly mediated by histo-blood group antigens (HBGAs), which function as a receptor or attachment factors on gut epithelial surfaces. HBGA synthesis is mediated by fucosyltransferases and glycosyltransferases under the genetic control of the FUT2 (secretor), FUT3 (Lewis), and ABO (H) genes on chromosome 19. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. This genetic diversity has an effect on genotype-specific susceptibility, molecular epidemiology, and vaccine take. Here, we will discuss studies on genetic susceptibility to rotavirus infection and place them in the context of population susceptibility, rotavirus epidemiology, vaccine take, and public health impact.

  • 27.
    Sharma, Sumit
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi.
    Hagbom, Marie
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi.
    Nordgren, Johan
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi.
    Frodlund, Jonas
    Vastervik Hosp, Sweden.
    Hinkula, Jorma
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Logopedi, Audiologi och Otorhinolaryngologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken.
    Svensson, Lennart
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Karolinska Inst, Sweden.
    Detection of rotavirus- and norovirus-specific IgG memory B cells in tonsils2019Ingår i: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 91, nr 2, s. 326-329Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Because rotavirus (RV) and norovirus (NoV) are transmitted through the fecal-oral route, tonsils due to their location within the oropharynx may sample or become infected with these viruses. We investigated if RV and NoV RNA/antigen, or virus-specific memory/plasma B cells can be detected in the tonsils. While neither RV/NoV antigen, nor genomic RNA was detected, 90% (27/30) of tonsils tested had RV- and NoV-specific IgG memory B cells. However, the mechanism explaining how these cells get there (whether because of local induction or homing after induction at other sites) and the role these cells might play during active infection is not yet clear.

  • 28.
    Nordgren, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Genetic Susceptibility to Human Norovirus Infection: An Update2019Ingår i: Viruses, E-ISSN 1999-4915, Vol. 11, nr 3, artikel-id 226Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Noroviruses are the most common etiological agent of acute gastroenteritis worldwide. Despite their high infectivity, a subpopulation of individuals is resistant to infection and disease. This susceptibility is norovirus genotype-dependent and is largely mediated by the presence or absence of human histo-blood group antigens (HBGAs) on gut epithelial surfaces. The synthesis of these HBGAs is mediated by fucosyl- and glycosyltransferases under the genetic control of the FUT2 (secretor), FUT3 (Lewis) and ABO(H) genes. The so-called non-secretors, having an inactivated FUT2 enzyme, do not express blood group antigens and are resistant to several norovirus genotypes, including the predominant GII.4. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. Here, we review previous in vivo studies on genetic susceptibility to norovirus infection. These are discussed in relation to population susceptibility, vaccines, norovirus epidemiology and the impact on public health.

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  • 29.
    Bucardo, Filemon
    et al.
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Reyes, Yaoska
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Rönnelid, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Histo-blood group antigens and rotavirus vaccine shedding in Nicaraguan infants2019Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 9, artikel-id 10764Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (= 3, 4-7 and = 8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at = 4 days post vaccination (DPV). At = 4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (amp;gt;13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.

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  • 30.
    Piedade, Joao
    et al.
    Univ Nova Lisboa, Portugal.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Esteves, Filipa
    Univ Nova Lisboa, Portugal.
    Esteves, Aida
    Univ Nova Lisboa, Portugal.
    Teodosio, Rosa
    Univ Nova, Portugal.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Istrate, Claudia
    Univ Nova Lisboa, Portugal.
    Molecular epidemiology and host genetics of norovirus and rotavirus infections in Portuguese elderly living in aged care homes2019Ingår i: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 91, nr 6, s. 1014-1021Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Norovirus (NoV) and rotavirus group A (RVA) are major agents of acute gastroenteritis worldwide. This study aimed to investigate their epidemiological profile in Portuguese elderly living in long-term care facilities and to assess the host genetic factors mediating infection susceptibility. From November 2013 to June 2015, 636 faecal specimens from 169 elderly, mainly asymptomatic, living in nursing homes in Greater Lisbon and Faro district, Portugal, were collected. NoV and RVA were detected by real-time polymerase chain reaction and NoV genotyped by phylogenetic analysis. NoV detection rate was 7.1% (12 of 169). Three GI.3 and one GII.6 strains were genotyped. RVA detection rate was 3.6% (6 of 169), exclusively in asymptomatic individuals. Host genetic factors associated with infection susceptibility were described on 250 samples by saliva-based enzyme-linked immunosorbent assays. The Lewis-negative phenotype was 8.8% (22 of 250) and the rate of nonsecretors was 16.8% (42 of 250). Association to NoV and RVA infection was performed in the subgroup of individuals (n = 147) who delivered both faecal and saliva samples. The majority of NoV- and RVA-positive individuals (90.9% and 83.3%, respectively) were secretor-positive, with Lewis B phenotype. In a subset of individuals, FUT2 and FUT3 genes were genotyped to assess mutations and validate the secretor and Lewis phenotypes. All sequenced nonsecretors were homozygous for FUT2 nonsense mutation G428A. In this study, low detection rates of NoV and RVA infections were found during two winter seasons. However, even in the absence of any outbreak, the importance of finding these infections in a nonepidemic situation in long-term care facilities may have important implications for infection control.

  • 31.
    Baroni de Moraes, Marcia Terezinha
    et al.
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Olivares Olivares, Alberto Ignacio
    Univ Fed Roraima, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Fialho, Alexandre Madi
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Malta, Fabio Correia
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    da Silva e Mouta Junior, Sergio
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Bispo, Romanul de Souza
    Univ Fed Roraima, Brazil.
    Velloso, Alvaro Jorge
    Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Alves Leitao, Gabriel Azevedo
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Cantelli, Carina Pacheco
    Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Nordgren, Johan
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi.
    Svensson, Lennart
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi.
    Miagostovich, Marize Pereira
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Gagliardi Leite, Jose Paulo
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Phenotyping of Lewis and secretor HBGA from saliva and detection of new FUT2 gene SNPs from young children from the Amazon presenting acute gastroenteritis and respiratory infection2019Ingår i: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 70, s. 61-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker. In this study, Lewis and secretor HBGA phenotyping was performed using 352 saliva samples collected from children between three months and five years old born in the Amazon (Brazil, Venezuela and English Guyana) presenting AGE or acute respiratory infection (ARI), the latter considered as control samples. The total of children phenotyped as secretors was 323, corresponding to 91.80%. From these, 207 (58.80%) had a Le (a + b +) profile. The HBGA profiles were equally found in children with AGE as well as with ARI. The rs1047781 of the FUT2 gene was not detected in DNA from saliva cells with a Le (a + b +) profile. However, mutations not yet described in the FUT2 gene were observed: missense 325A amp;gt; T, 501C amp;gt; T, 585C amp;gt; T, 855A amp;gt; T and missense substitutions 327C amp;gt; T [S (Ser) amp;gt; C (Cys)], 446 T amp;gt; C [L(Leu) amp;gt; P(Pro)], 723C amp;gt; A [N(Asn) amp;gt; K(Lys)], 724A amp;gt; T [I(Ile) amp;gt; F(Phe)], 736C amp;gt; A [H(His) amp;gt; N(Asn)]. The SNP distribution in the FUT2 gene of the analyzed samples was very similar to that described in Asian populations, including indigenous tribes.

  • 32.
    Esteves, A.
    et al.
    Univ Nova Lisboa, Portugal.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Tavares, C.
    Univ Nova Lisboa, Portugal.
    Fortes, F.
    DNSP, Angola.
    Dimbu, R.
    DNSP, Angola.
    Saraiva, N.
    DNSP, Angola.
    Istrate, C.
    Univ Nova Lisboa, Portugal.
    Genetic diversity of norovirus in children under 5 years of age with acute gastroenteritis from Angola2018Ingår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 146, nr 5, s. 551-557Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Norovirus (NoV) is a major cause of acute gastroenteritis (AGE). In this study, we investigated the genetic diversity of NoV strains identified in children under 5 years of age with AGE in four provinces of Angola. Faecal samples from 343 children were screened for NoV by an in house real-time PCR assay and genotyping was performed by partial capsid gene sequencing. NoV was detected in 17.4% (58/334) of the samples, with high detection rates in children amp;lt;6 months old (19%) and in children aged 12-24 months (23%). Genotype diversity was large, as demonstrated by the 11 identified genotypes. GII.4 was the predominant genotype (20% of all NoV-positive samples), followed by GII.6 (15%), GI.3 (12%), GII.7 (10%) and by other genotypes to a lesser extent. Two GII.4 variants, New Orleans 2009 and Sydney 2012, were detected and several genetic clusters were observed for genotypes GI.3, GII.6 and GII.7. The present study shows high detection rates and genetic diversity of circulating NoV genotypes in paediatric AGE samples from Angola. This information emphasises the importance of continuous assessment of NoV burden and evolution in the target population.

  • 33.
    Barbe, Laure
    et al.
    Univ Nantes, France.
    Le Moullac-Vaidye, Beatrice
    Univ Nantes, France.
    Echasserieau, Klara
    Univ Nantes, France; Univ Nantes, France.
    Bernardeau, Karine
    Univ Nantes, France; Univ Nantes, France.
    Carton, Thomas
    Biofortis, France.
    Bovin, Nicolai
    RAS, Russia.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Ruvoen-Clouet, Nathalie
    Univ Nantes, France; Oniris, France.
    Le Pendu, Jacques
    Univ Nantes, France.
    Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 12961Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAc beta 3Gal beta 4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.

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  • 34.
    Westerberg, Sonja
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hagbom, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Rajan, Anandi
    Umea Univ, Sweden.
    Loitto, Vesa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Persson, B. David
    Umea Univ, Sweden.
    Allard, Annika
    Umea Univ, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Arnberg, Niklas
    Umea Univ, Sweden.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells2018Ingår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 92, nr 7, artikel-id e00026-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells. IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41 infection on human enterochromaffin cells and found it stimulates serotonin secretion in the cells, which is involved in regulation of intestinal secretion and gut motility and can also activate enteric glia cells, which are found in close proximity to enterochromaffin cells in vivo. This disruption of gut barrier homeostasis as maintained by these cells following human adenovirus 41 infection might be a mechanism in enteric adenovirus pathogenesis in humans and could indicate a possible serotonin-dependent cross talk between human adenovirus 41, enterochromaffin cells, and enteric glia cells.

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  • 35.
    Bonkoungou, Isidore Juste O.
    et al.
    Univ Ouaga, Burkina Faso; Natl Publ Hlth Lab, Burkina Faso.
    Ouedraogo, Nafissatou
    Univ Ouaga, Burkina Faso.
    Tamini, Laure
    Univ Ouaga, Burkina Faso; Charles de Gaulle Pediat Univ Hosp, Burkina Faso.
    Teguera, Rabieta Kouboura
    Natl Publ Hlth Lab, Burkina Faso.
    Yameogo, Pouire
    Natl Publ Hlth Lab, Burkina Faso.
    Drabo, Maxime Koine
    Natl Publ Hlth Lab, Burkina Faso.
    Medah, Isaie
    Minist Hlth, Burkina Faso.
    Barro, Nicolas
    Univ Ouaga, Burkina Faso.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Rotavirus and norovirus in children with severe diarrhea in Burkina Faso before rotavirus vaccine introduction2018Ingår i: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 90, nr 9, s. 1453-1460Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Burkina Faso introduced rotavirus vaccine (RotaTeq) to the national immunization program in November 2013. This study describes the detection rates, clinical profiles, and molecular epidemiology of rotavirus and norovirus (NoV) infections among children amp;lt;5 years hospitalized (n=154) because of acute diarrhea in Ouagadougou, Burkina Faso, from December 2012 to November 2013, just before the start of vaccination. Overall, 44% and 23% of fecal samples were positive for rotavirus and NoV, respectively, most of them detected during the cold dry season (December-March). The predominant G/P combinations were G12P[8] (47%) and G6P[6] (30%). G2P[4] (n=3), G12P[6] (n=3), and G6P[8] (n=1) werealso detected. Nearly all (94%) successfully genotyped NoV strains belonged to genotype GII.4. The predominance of rotavirus and NoV was noteworthy in the age group 6 months, with 67% rotavirus and 22% NoV, respectively. Vomiting was significantly more common among rotavirus-infected children. To conclude, this study shows high detection rates of both rotavirus and NoV in children with severe diarrhea in Burkina Faso just before the introduction of rotavirus group A vaccination. The results can be used for estimating the impact of rotavirus group A vaccination, which started in the end of 2013. Furthermore, this study shows that the G6P[6] rotavirus strains emerging in Burkina Faso in 2010 is now established as a regionally important genotype.

  • 36.
    Bucardo, Filemon
    et al.
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Reyes, Yaoska
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    The Lewis A phenotype is a restriction factor for Rotateq and Rotarix vaccine-take in Nicaraguan children2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 1502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Histo-blood group antigens (HBGAs) and the Lewis and secretor antigens are associated with susceptibility to rotavirus infection in a genotype-dependent manner. Nicaraguan children were prospectively enrolled in two cohorts vaccinated with either RotaTeq RV5 (n = 68) or Rotarix RV1 (n = 168). Lewis and secretor antigens were determined by saliva phenotyping and genotyping. Seroconversion was defined as a 4-fold increase in plasma IgA antibody titer 1 month after administration of the first dose of the vaccine. Regardless of the vaccine administered, significantly fewer of the children with Lewis A phenotype (0/14) seroconverted after receiving the first vaccine dose compared to 26% (45/175) of those with the Lewis B phenotype and 32% (15/47) of the Lewis negative individuals (P amp;lt; 0.01). Furthermore, following administration of the RV1 vaccine, secretor-positive ABO blood group B children seroconverted to a significantly lesser extent (5%) compared to secretor-positive children with ABO blood groups A (26%) and O (27%) (P amp;lt; 0.05). Other factors such as pre-vaccination titers, sex, breastfeeding, and calprotectin levels did not influence vaccine-take. Differences in HBGA expression appear to be a contributing factor in the discrepancy in vaccine-take and thus, in vaccine efficacy in different ethnic populations.

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  • 37.
    Ouermi, D.
    et al.
    Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA)/LABIOGENE, Université Ouaga I Professeur Joseph KI-ZERBO, 01 B.P. 364, 01 Ouagadougou, Ouagadougou, Burkina Faso, West Africa.
    Soubeiga, D.
    Institut de Formation et de Recherche Interdisciplinaires en Santé (IFRIS), Ouagadougou, Burkina Faso.
    Nadembega, W. M. C.
    Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA)/LABIOGENE, Université Ouaga I Professeur Joseph KI-ZERBO, 01 B.P. 364, 01 Ouagadougou, Ouagadougou, Burkina Faso, West Africa.
    Sawadogo, P. M.
    Institut de Formation et de Recherche Interdisciplinaires en Santé (IFRIS), Ouagadougou, Burkina Faso.
    Zohoncon, T. M.
    Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA)/LABIOGENE, Université Ouaga I Professeur Joseph KI-ZERBO, 01 B.P. 364, 01 Ouagadougou, Ouagadougou, Burkina Faso, West Africa.
    Obiri-Yeboah, D.
    Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Ghana.
    Djigma, F. W.
    Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA)/LABIOGENE, Université Ouaga I Professeur Joseph KI-ZERBO, 01 B.P. 364, 01 Ouagadougou, Ouagadougou, Burkina Faso, West Africa.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Simpore, J.
    University Saint Thomas dAquin, USTA, Ouagadougou, Burkina Faso.
    Molecular Epidemiology of Rotavirus in Children under Five in Africa (2006-2016): A Systematic Review2017Ingår i: Pakistan Journal of Biological Sciences, ISSN 1028-8880, E-ISSN 1812-5735, Vol. 20, nr 2, s. 59-69Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Group A human rotaviruses (RVA) are the most common causes of severe viral gastroenteritis in infants and young children worldwide. The available vaccines, while effective in Europe and North America have shown a reduced efficacy in Africa. One issue raised is the genetic variability of RVA. The objective of this study was to perform a literature review of molecular epidemiology to determine the prevalence of RVA genotypes circulating in Africa so as to establish a mapping of reliable data on these various genotypes. The search for articles was done from the National Institutes of Health (PUBMED) using three set of keywords. Articles were selected with inclusion criteria such as the date of publication, the age of the children, the sample size and the diagnostic techniques (standardized laboratory techniques). The data were imported into STATA SE version 11 software. Specific prevalence was estimated with Confidence Intervals (CI) of 95%. A total of 326 published studies were initially retrieved, out of which 27 studies were finally selected for the systematic review. The selected studies cover 20 African countries. The most encountered genotypes in Africa during this period were G1 (32.72%), followed by G2 (17.17%), G3 (9.88%), G9 (8.61%) and G12 (7.56%) among the G-types. The most common P-types were P[8] (48.71%) followed by P[6] (22.60%) and P[4] (11.58%) and the G1P[8] combination (22.64%) was the most encountered followed by G2P[4] (8.29%), G9P[8] (6.95%) and G2P[6] (5.00%). North Africa presented the highest prevalence of the P[8] genotype (65.70%). This review provides a comprehensive view of the current circulating rotavirus strains in Africa, which can be important in light of the new rotavirus vaccinations. Indeed, in Africa, the pursuit of national and continental studies for epidemiological surveillance of circulating rotavirus strains is vital for the promotion of future successful vaccines.

  • 38.
    Hagbom, Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Novak, Daniel
    Sahlgrens University Hospital, Sweden.
    Ekstrom, Malin
    Sahlgrens University Hospital, Sweden.
    Khalid, Younis
    Sahlgrens University Hospital, Sweden.
    Andersson, Maria
    University of Gothenburg, Sweden.
    Lindh, Magnus
    University of Gothenburg, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial2017Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 12, nr 10, artikel-id e0186824Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Rotavirus and norovirus cause acute gastroenteritis with severe diarrhoea and vomiting, symptoms that may lead to severe dehydration and death. The objective of this randomized double-blinded placebo-controlled study was to investigate whether ondansetron, a serotonin receptor antagonist could attenuate rotavirus-and norovirus-induced vomiting and diarrhoea, which would facilitate oral rehydration and possibly accelerate recovery and reduce need for hospitalization. Methods Children with acute gastroenteritis, aged 6 months to 16 years where enrolled (n = 104) and randomized to one single oral dose (0.15mg/kg) of ondansetron (n = 52) or placebo (n = 52). The number of diarrhoea and vomiting episodes during the 24 hours following treatment was reported as well as the number of days with symptoms. Pathogens in faeces were diagnosed by real-time PCR. Outcome parameters were analyzed for rotavirus-and noroviruspositive children. Results One dose of oral ondansetron reduced duration of rotavirus clinical symptoms (p = 0.014), with a median of two days. Furthermore, ondansetron reduced diarrhea episodes, most pronounced in children that had been sick for more than 3 days before treatment (p = 0.028). Conclusion Ondansetron may be a beneficial treatment for children with rotavirus gastroenteritis.

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  • 39.
    Bucardo, Filemon
    et al.
    National Autonomous University of Nicaragua, Nicaragua.
    Reyes, Yaoska
    National Autonomous University of Nicaragua, Nicaragua.
    Becker-Dreps, Sylvia
    University of N Carolina, NC USA.
    Bowman, Natalie
    University of N Carolina, NC USA.
    Gruber, Joann F.
    University of N Carolina, NC USA.
    Vinje, Jan
    National Centre Immunizat and Resp Disease, GA USA.
    Espinoza, Felix
    National Autonomous University of Nicaragua, Nicaragua.
    Paniagua, Margarita
    National Autonomous University of Nicaragua, Nicaragua.
    Balmaseda, Angel
    Minist Heatlh, Nicaragua.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Pediatric norovirus GII.4 infections in Nicaragua, 1999-20152017Ingår i: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 55, s. 305-312Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. Methods: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children amp;lt;= 7 years with AGE from 6 hospitals in Nicaragua (n = 538), and 3 community clinics (n = 919) and households (n = 333) in Leon, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n = 162) and households (n = 105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. Results: Norovirus was found in 19% (n = 338) and 12% (n = 32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12 months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. Conclusions: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12 months of age, implicating GII.4 as the main norovirus vaccine target.

  • 40.
    Henningsson, A. J.
    et al.
    Regional Jönköping County, Sweden.
    Nilsson Bowers, A.
    Regional Jönköping County, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Quttineh, M.
    Regional Jonköping County, Sweden.
    Matussek, A.
    Regional Jonköping County, Sweden; Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Haglund, S.
    Regional Jonköping County, Sweden.
    Rapid diagnosis of acute norovirus-associated gastroenteritis: evaluation of the Xpert Norovirus assay and its implementation as a 24/7 service in three hospitals in Jonkoping County, Sweden2017Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, nr 10, s. 1867-1871Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Noroviruses are a leading cause of epidemic and sporadic cases of acute gastroenteritis worldwide. The rapid diagnosis of norovirus infection is important for prompt infection control measures and may reduce the need for additional diagnostic testing. Here we evaluated the performance of the rapid Xpert Norovirus assay, and assessed the turn-around time (TAT) before and after the implementation of the analysis as a 24/7 service at all the three hospitals in Jonkoping County, Sweden. We describe the implementation process which was performed in two steps during 2014. A total number of 276 clinical samples (stool and vomitus) from patients with symptoms of acute gastroenteritis were included in 2014-2015. The samples were analysed with the Xpert Norovirus assay and the already existing routine method: an in-house reverse transcription real-time PCR. Samples showing discrepant results with the two assays were further analysed by a third PCR method. The Xpert Norovirus assay performed well with a sensitivity of 100% and a specificity of 93% compared to the gold standard (defined as the result obtained by at least two of the three PCR methods). The median TAT decreased from 22 hours in 2013 to 2.4 hours in 2015 (p amp;lt; 0.001). We conclude that the performance of the Xpert Norovirus assay was excellent, and that the implementation of the analysis as a 24/7 service at all three hospitals in the county has greatly reduced the time to diagnosis which is beneficial for both patients and healthcare providers.

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  • 41.
    Gunaydin, Gokce
    et al.
    Karolinska Institute, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hammarstrom, Lennart
    Karolinska Institute, Sweden.
    Association of elevated rotavirus-specific antibody titers with HBGA secretor status in Swedish individuals: The FUT2 gene as a putative susceptibility determinant for infection2016Ingår i: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 211, s. 64-68Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The histo-blood group antigens (HBGAs) have recently been suggested to serve as attachment factors for rotavirus VP8* (P-genotype) in vitro and associated with susceptibility in vivo. We thus investigated whether rotavirus antibody titers and genotype specific neutralization titers correlate with HBGA status in Swedish individuals. We investigated the effect of inactivating mutations in the secretor FUT2 (rs601338) and Lewis FUT3 genes (rs28362459, rs3894326, rs812936 and rs778986) on serum IgG antibody titers and neutralizing antibody titers to rotavirus strains of the P[8] and P[6] genotypes in Swedish healthy blood donors and patients with IgA deficiency using genotyping, enzyme linked immunosorbent assay and a neutralization assay. Rotavirus-specific serum IgG and neutralizing antibody titers to the Wa strain (G1P[8]), but not to the ST3 (G4P[6]) strain, were significantly higher in secretors (with at least one functional FUT2 gene) than in non-secretors (P<0.001) (with homozygous nonsense mutation in the FUT2 gene). Thus, our results represent that secretors show elevated rotavirus specific serum antibodies, suggesting a higher susceptibility to rotavirus infections, as compared to non-secretors in Sweden. (C) 2015 Elsevier B.V. All rights reserved.

  • 42.
    Nordgren, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Kambhampati, Anita
    Centre Disease Control and Prevent, USA.
    Lopman, Ben
    Centre Disease Control and Prevent, USA.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Innate Resistance and Susceptibility to Norovirus Infection2016Ingår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 12, nr 4, s. e1005385-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

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  • 43.
    Esteves, Aida
    et al.
    NOVA University of Lisbon, Portugal.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Pereira, Joana
    NOVA University of Lisbon, Portugal.
    Fortes, Filomeno
    National Institute Public Heatlh, Angola.
    Dimbu, Rafael
    National Institute Public Heatlh, Angola.
    Saraiva, Nilton
    National Institute Public Heatlh, Angola.
    Mendes, Cristina
    NOVA University of Lisbon, Portugal.
    Istrate, Claudia
    NOVA University of Lisbon, Portugal.
    Molecular Epidemiology of Rotavirus in Four Provinces of Angola Before Vaccine Introduction2016Ingår i: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 88, nr 9, s. 1511-1520Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. (C) 2016 Wiley Periodicals, Inc.

  • 44.
    Bialowas, Sonja
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hagbom, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Thommie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Rotavirus and Serotonin Cross-Talk in Diarrhoea2016Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 11, nr 7, s. e0159660-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNA(NSP4)) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNA(VP4), siRNA(VP6) and siRNA(VP7). Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p amp;lt; 0.05) less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9). Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p amp;lt; 0.05). A most surprising finding was that the serotonin receptor antagonist significantly (p amp;lt; 0.05) also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron.

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  • 45.
    Bucardo, F.
    et al.
    National Autonomous University of Leon UNAN Leon, Nicaragua.
    Gonzalez, F.
    National Autonomous University of Leon UNAN Leon, Nicaragua.
    Reyes, Y.
    National Autonomous University of Leon UNAN Leon, Nicaragua.
    Blandon, P.
    National Autonomous University of Leon UNAN Leon, Nicaragua.
    Saif, L.
    Ohio State University, OH USA.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Seroprevalence in Household Raised Pigs Indicate High Exposure to GII Noroviruses in Rural Nicaragua2016Ingår i: Zoonoses and Public Health, ISSN 1863-1959, E-ISSN 1863-2378, Vol. 63, nr 8, s. 600-607Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Information about porcine norovirus (PoNoV), genetically similar to human NoV (HuNoV), is limited from rural areas where household-raised pigs are heavily exposed to faecal material which could facilitate transmission. Histoblood group antigens (HBGAs) are known susceptibility factors to NoV in humans and in a germfree piglet model but their role in susceptibility in the porcine population remains unknown. This study reports: (i) the seroprevalence and antibody titres to human norovirus (NoV) VLPs in household raised pigs; (ii) the distribution of HBGAs in relation to NoV IgG antibody titres and further characterization by blocking of GII. 4 VLP binding to pig gastric mucins (PGM). The majority of pigs were seropositive to all three VLPs tested (58-70%) with seropositivity and cross-reactivity increasing significantly with age. However, pig sera could not block the binding of NoV GII. 4 VLPs (Dijon) to PGM suggesting no previous infection with this genotype. The majority of the pigs were H-positive (84%), a susceptibility factor for human infections. IgG antibody titres were however higher in H-negative (GMT = 247) as compared with H-positive (GMT = 57) pigs, but after age stratification, this difference in antibody titres was only observed in pigs = 1 month of age. In conclusion, serological data show that the porcine population of Nicaragua is highly exposed to NoV infections, and the association to HBGAs warrants further investigation.

  • 46.
    Gia Phan, Tung
    et al.
    Blood Syst Research Institute, CA 94118 USA; University of Calif San Francisco, CA 94118 USA.
    Charlys da Costa, Antonio
    Blood Syst Research Institute, CA 94118 USA; University of Sao Paulo, Brazil.
    del Valle Mendoza, Juana
    University of Peruana Ciencias Aplicadas UPC, Peru.
    Bucardo-Rivera, Filemon
    Institute Invest Nutr, Peru; University of Leon, Nicaragua.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    ORyan, Miguel
    University of Chile, Chile.
    Deng, Xutao
    Blood Syst Research Institute, CA 94118 USA.
    Delwart, Eric
    Blood Syst Research Institute, CA 94118 USA; University of Calif San Francisco, CA 94118 USA.
    The fecal virome of South and Central American children with diarrhea includes small circular DNA viral genomes of unknown origin2016Ingår i: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 161, nr 4, s. 959-966Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Viral metagenomics of feces collected from 58 Peruvian children with unexplained diarrhea revealed several small circular ssDNA genomes. Two genomes related to sequences previously reported in feces from chimpanzees and other mammals and recently named smacoviruses were characterized and then detected by PCR in 1.7 % (1/58) and 19 % (11/58) of diarrheal samples, respectively. Another three genomes from a distinct small circular ssDNA viral group provisionally called pecoviruses encoded Cap and Rep proteins with < 35 % identity to those in related genomes reported in human, seal, porcine and dromedary feces. Pecovirus DNA was detected in 15.5 % (9/58), 5.9 % (3/51) and 3 % (3/100) of fecal samples from unexplained diarrhea in Peru, Nicaragua and Chile, respectively. Feces containing these ssDNA genomes also contained known human enteric viral pathogens. The cellular origins of these circular ssDNA viruses, whether human cells, ingested plants, animals or fungal foods, or residents of the gut microbiome, are currently unknown.

  • 47.
    Sharma, Sumit
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Editorial Material: Rotavirus vaccines in developing countries: issues and future considerations in FUTURE VIROLOGY, vol 10, issue 6, pp 663-6662015Ingår i: FUTURE VIROLOGY, ISSN 1746-0794, Vol. 10, nr 6, s. 663-666Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 48.
    de Graaf, M.
    et al.
    Erasmus MC, Netherlands.
    van Beek, J.
    Erasmus MC, Netherlands; National Institute Public Health and Environm RIVM, Netherlands.
    Vennema, H.
    National Institute Public Health and Environm RIVM, Netherlands.
    Podkolzin, A. T.
    Minist Public Health Russia, Russia.
    Hewitt, J.
    Institute Environm Science and Research, New Zealand.
    Bucardo, F.
    University of Leon, Nicaragua.
    Templeton, K.
    Royal Infirm Edinburgh NHS Trust, Scotland.
    Mans, J.
    University of Pretoria, South Africa.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Reuter, G.
    ANTSZ Regional Institute State Public Health Serv, Hungary.
    Lynch, M.
    Mater Misericordiae University Hospital, Ireland.
    Rasmussen, L. D.
    Statens Serum Institute, Denmark.
    Iritani, N.
    Osaka City Institute Public Health and Environm Science, Japan.
    Chan, M. C.
    Chinese University of Hong Kong, Peoples R China.
    Martella, V.
    University of Aldo Moro Bari, Italy.
    Ambert-Balay, K.
    CHU Dijon, France.
    Vinje, J.
    Centre Disease Control and Prevent, GA USA.
    White, P. A.
    University of New S Wales, Australia.
    Koopmans, M. P.
    Erasmus MC, Netherlands; National Institute Public Health and Environm RIVM, Netherlands.
    Emergence of a novel GII.17 norovirus - End of the GII.4 era?2015Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, nr 26, s. 21178-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus.

  • 49.
    Istrate, Claudia
    et al.
    University of Nova Lisboa, Portugal.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Videira e Castro, Sandra
    University of Nova Lisboa, Portugal.
    Lopes, Angela
    University of Nova Lisboa, Portugal.
    Piedade, Joao
    University of Nova Lisboa, Portugal.
    Zaky, Ahmed
    Institute Marques de Valle Flor, Portugal.
    Lima, Antonio
    Institute Marques de Valle Flor, Sao Tome and Prin; Minist Saude, Sao Tome and Prin.
    Neves, Edgar
    Institute Marques de Valle Flor, Sao Tome and Prin.
    Veiga, Jose
    Institute Marques de Valle Flor, Sao Tome and Prin; Minist Saude, Sao Tome and Prin.
    Esteves, Aida
    University of Nova Lisboa, Portugal.
    High rate of detection of G8P[6] rotavirus in children with acute gastroenteritis in So Tom, and Principe2015Ingår i: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 160, nr 2, s. 423-428Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The burden of rotavirus infections greatly affects the low-income African countries. In the absence of epidemiological data on pediatric diarrhea in So Tom, and Principe (STP), a study was conducted from August to December 2011. Rotavirus antigen was detected in 36.7 % of the collected fecal samples (87/237). G8P[6] was identified as the predominant genotype (71.1 % detection rate), while G1P[8] represented only 8.4 %. Phylogenetic analysis of VP7 G8 strains showed clustering within lineage G8d, while VP4 P[6] strains clustered within lineage 1a. Our results represent the first report on rotavirus from STP and show one of the highest detection rates of G8 rotaviruses worldwide.

  • 50.
    Bucardo, Filemon
    et al.
    National Autonomous University of Leon, Nicaragua.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Impact of vaccination on the molecular epidemiology and evolution of group A rotaviruses in Latin America and factors affecting vaccine efficacy2015Ingår i: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 34, s. 106-113Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Despite high rotavirus (RV) vaccine coverage (similar to 83%) and good effectiveness (similar to 77%) against RV-diarrhea hospitalization, RV is still contributing to the burden of diarrhea that persists in hospital settings in several Latin American countries, where RV vaccination is being implemented. Due to the extensive genomic and antigenic diversity, among co-circulating human RV, a major concern has been that the introduction of RV vaccination could exert selection pressure leading to higher prevalence of strains not included in the vaccines and/or emergence of new strains, thus, reducing the efficacy of vaccination. Here we review the molecular epidemiology of RV in Latin America and explore issues of RV evolution and selection in light of vaccination. We further explore etiologies behind the large burden of diarrhea remaining after vaccination in some countries and discuss plausible reasons for vaccine failures. (C) 2015 Elsevier B.V. All rights reserved.

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