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Sharma, Sumit
Publications (9 of 9) Show all publications
Gunaydin, G., Nordgren, J., Sharma, S. & Hammarstrom, L. (2016). Association of elevated rotavirus-specific antibody titers with HBGA secretor status in Swedish individuals: The FUT2 gene as a putative susceptibility determinant for infection. Virus Research, 211, 64-68
Open this publication in new window or tab >>Association of elevated rotavirus-specific antibody titers with HBGA secretor status in Swedish individuals: The FUT2 gene as a putative susceptibility determinant for infection
2016 (English)In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 211, p. 64-68Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2016
Keywords
Rotavirus; Histo-blood group antigen (HBGA); FUT2; Lewis; Secretor; Antibody response
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124088 (URN)10.1016/j.virusres.2015.10.005 (DOI)000366443500009 ()26454189 (PubMedID)
Note

Funding Agencies|Swedish Research Council [K2012-56X-05975-32-3]

Available from: 2016-01-25 Created: 2016-01-19 Last updated: 2017-11-30
Nordgren, J., Sharma, S., Kambhampati, A., Lopman, B. & Svensson, L. (2016). Innate Resistance and Susceptibility to Norovirus Infection. PLoS Pathogens, 12(4), e1005385
Open this publication in new window or tab >>Innate Resistance and Susceptibility to Norovirus Infection
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2016 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 12, no 4, p. e1005385-Article in journal (Refereed) Published
Abstract [en]

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Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-130446 (URN)10.1371/journal.ppat.1005385 (DOI)000378156900003 ()27115484 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research

Available from: 2016-08-06 Created: 2016-08-05 Last updated: 2017-11-28
Sharma, S. & Nordgren, J. (2015). Editorial Material: Rotavirus vaccines in developing countries: issues and future considerations in FUTURE VIROLOGY, vol 10, issue 6, pp 663-666. FUTURE VIROLOGY, 10(6), 663-666
Open this publication in new window or tab >>Editorial Material: Rotavirus vaccines in developing countries: issues and future considerations in FUTURE VIROLOGY, vol 10, issue 6, pp 663-666
2015 (English)In: FUTURE VIROLOGY, ISSN 1746-0794, Vol. 10, no 6, p. 663-666Article in journal, Editorial material (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
FUTURE MEDICINE LTD, 2015
Keywords
histo-blood group antigen; neonates; P[6]; rotavirus; vaccine efficacy
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120296 (URN)10.2217/fvl.15.32 (DOI)000357132100002 ()
Available from: 2015-07-24 Created: 2015-07-24 Last updated: 2015-07-24
Istrate, C., Sharma, S., Nordgren, J., Videira e Castro, S., Lopes, A., Piedade, J., . . . Esteves, A. (2015). High rate of detection of G8P[6] rotavirus in children with acute gastroenteritis in So Tom, and Principe. Archives of Virology, 160(2), 423-428
Open this publication in new window or tab >>High rate of detection of G8P[6] rotavirus in children with acute gastroenteritis in So Tom, and Principe
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2015 (English)In: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 160, no 2, p. 423-428Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-115324 (URN)10.1007/s00705-014-2244-7 (DOI)000349433500006 ()25283609 (PubMedID)
Note

Funding Agencies|Ministry of Health of STP; Calouste Gulbenkian Foundation (Lisbon, Portugal)

Available from: 2015-03-13 Created: 2015-03-13 Last updated: 2017-12-04
Nordgren, J., Sharma, S., Bucardo, F., Nasir, W., Gunaydin, G., Ouermi, D., . . . Svensson, L. (2014). Both Lewis and Secretor Status Mediate Susceptibility to Rotavirus Infections in a Rotavirus Genotype-Dependent Manner. Clinical Infectious Diseases, 59(11), 1567-1573
Open this publication in new window or tab >>Both Lewis and Secretor Status Mediate Susceptibility to Rotavirus Infections in a Rotavirus Genotype-Dependent Manner
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2014 (English)In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 59, no 11, p. 1567-1573Article in journal (Refereed) Published
Abstract [en]

Background. The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo-blood group antigens (HBGAs) in an RV genotype-dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy. Methods. Association between HBGAs status and susceptibility to RV P genotypes was investigated in children in Burkina Faso and Nicaragua. In total, 242 children with diarrhea in Burkina Faso and Nicaragua were investigated, 93 of whom were RV positive. Results. In Burkina Faso, the P[8] RV strains (n = 27) infected only Lewis-and secretor-positive children (27/27; P less than .0001), but no Lewis-negative children. In contrast, the P[6] strains (n = 27) infected predominantly Lewis-negative children (n = 18; P less than.0001) but also Lewis-positive children, irrespective of their secretor status. The results from Nicaragua confirmed that all P[8]-infected children (n = 22) were secretor Lewis positive. Conclusions. As VP4 of genotype P[8] is a component of current RV vaccines, our finding that Lewis-negative children are resistant to P[8] strains provides a plausible explanation for the reduced vaccine efficacy in populations with a high percentage of Lewis-negative individuals, such as in Africa. Furthermore, our findings provide a plausible explanation as to why P[6] RV strains are more common in Africa.

Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy A1 - Oxford Open Option C, 2014
Keywords
rotavirus; histo-blood group antigen; Lewis; susceptibility; vaccine
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113179 (URN)10.1093/cid/ciu633 (DOI)000345841900011 ()25097083 (PubMedID)
Note

Funding Agencies|Swedish Research Council [8266, 3485, dnr-348-2011-7420]

Available from: 2015-01-13 Created: 2015-01-12 Last updated: 2017-12-05
Mansoori, N., Tripathi, M., Alam, R., Luthra, K., Sharma, S., Lakshmy, R., . . . Mukhopadhyay, A. K. (2014). Serum Folic Acid and RFC A80G Polymorphism in Alzheimers Disease and Vascular Dementia. American Journal of Alzheimer’s Disease and Other Dementia, 29(1), 38-44
Open this publication in new window or tab >>Serum Folic Acid and RFC A80G Polymorphism in Alzheimers Disease and Vascular Dementia
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2014 (English)In: American Journal of Alzheimer’s Disease and Other Dementia, ISSN 1533-3175, E-ISSN 1938-2731, Vol. 29, no 1, p. 38-44Article in journal (Refereed) Published
Abstract [en]

Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2.4 (95% confidence interval [CI]: 1.4-4.5) times higher odds of having AD and 2.1 (95% CI: 1.1-4.2) times higher odds of having VaD than patients having folic acid ≥8.45 ng/mL. Serum vitamin B12 level did not show any such statistically significant effect in altering the odds. No direct association was found between variant (G) allele or genotype of rs1051266 with AD and VaD cases. On serum folate level no association was observed with gene polymorphism.

Place, publisher, year, edition, pages
SAGE Publications (UK and US), 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-107465 (URN)10.1177/1533317513505131 (DOI)000331463000006 ()2-s2.0-84896735112 (Scopus ID)
Available from: 2014-06-12 Created: 2014-06-12 Last updated: 2017-12-05
Nordgren, J., Juste O Bonkoungou, I., Nitiema, L. W., Sharma, S., Ouermi, D., Simpore, J., . . . Svensson, L. (2012). Rotavirus in diarrheal children in rural Burkina Faso: High prevalence of genotype G6P[6]. Infection, Genetics and Evolution, 12(8), 1892-1898
Open this publication in new window or tab >>Rotavirus in diarrheal children in rural Burkina Faso: High prevalence of genotype G6P[6]
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2012 (English)In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 12, no 8, p. 1892-1898Article in journal (Refereed) Published
Abstract [en]

Group A rotavirus (RVA) is the most common cause of severe gastroenteritis in young children globally, and responsible for a significant number of deaths in African countries. While vaccines are available, trials have shown a lesser efficacy in Africa. One of the reasons could be the prevalence and/or emergence of unusual or novel RVA strains, as many strains detected in African countries remain uncharacterized. less thanbrgreater than less thanbrgreater thanIn this study, we characterized RVA positive specimens from two remote rural areas in Burkina Faso, West Africa. In total 56 RVA positive specimens were subgrouped by their VP6 gene, and G-and P typed by PCR and/or sequencing of the VP7 and VP4 genes, respectively. less thanbrgreater than less thanbrgreater thanNotably, we found a high prevalence of the unusual G6P[6]SGI strains (23%). It was the second most common constellation after G9P[8]SGII (32%); and followed by G1P[8]SGII (20%) and G2P[4]SGI (9%). We also detected a G8P[6]SGI strain, for the first time in Burkina Faso. The intra-genetic diversity was high for the VP4 gene with two subclusters within the P[8] genotype and three subclusters within the P[6] genotype which were each associated with a specific G-type, thereby suggesting a genetic linkage. The G6P[6]SGI and other SGI RVA strains infected younger children as compared to SGII strains (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanTo conclude, in this study we observed the emergence of unusual RVA strains and high genetic diversity of RVA in remote rural areas of Burkina Faso. The results highlight the complexity of RVA epidemiology which may have implication for the introduction of rotavirus vaccines currently being evaluated in many African countries.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Rotavirus, Genotypes, G6P[6], Rural areas, Gastroenteritis, Children
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-87464 (URN)10.1016/j.meegid.2012.08.014 (DOI)000312429000038 ()
Note

Funding Agencies|Swedish Research Council|10392|

Available from: 2013-01-18 Created: 2013-01-18 Last updated: 2017-12-06Bibliographically approved
Hagbom, M., Sharma, S., Lundgren, O. & Svensson, L. (2012). Towards a human rotavirus disease model. CURRENT OPINION IN VIROLOGY, 2(4), 408-418
Open this publication in new window or tab >>Towards a human rotavirus disease model
2012 (English)In: CURRENT OPINION IN VIROLOGY, ISSN 1879-6257, Vol. 2, no 4, p. 408-418Article in journal (Refereed) Published
Abstract [en]

While the clinical importance of human rotavirus (RV) disease is well recognized and potent vaccines have been developed, our understanding of how human RV causes diarrhoea, vomiting and death remains unresolved. The fact that oral rehydration corrects electrolyte and water loss, indicates that enterocytes in the small intestine have a functional sodium-glucose co-transporter. Moreover, RV infection delays gastric emptying and loperamide appears to attenuate RV diarrhoea, thereby suggesting activation of the enteric nervous system. Serotonin (5-HT) receptor antagonists attenuate vomiting in young children with gastroenteritis while zinc and enkephalinase inhibitors attenuate RV-induced diarrhoea. In this review we discuss clinical symptoms, pathology, histology and treatment practices for human RV infections and compile the data into a simplified disease model.

Place, publisher, year, edition, pages
Elsevier, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-86900 (URN)10.1016/j.coviro.2012.05.006 (DOI)000312112900006 ()
Note

Funding Agencies|Swedish Research Council|A0320301|

Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2013-01-07
Bialowas, S., Hagbom, M., Karlsson, T., Nordgren, J., Sharma, S., Magnusson, K.-­. & Svensson, L.Intracellularly expressed rotavirus NSP4 stimulates release of serotonin (5-HT) from human enterochromaffin cells.
Open this publication in new window or tab >>Intracellularly expressed rotavirus NSP4 stimulates release of serotonin (5-HT) from human enterochromaffin cells
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Rotavirus (RV) is associated with diarrhoea and vomiting, but the mechanisms behind these symptoms remain unresolved. While RV have been shown to infect and stimulate secretion of serotonin (5-hydroxytryptamine; 5-HT) 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 (VP) being responsible for this novel property.

To address this issue, human EC cells were transfected with small interfering RNA (siRNA) targeting the structural (VP4, VP6 and VP7) and the non-structural protein 4 (NSP4) followed by infection with Rhesus rotavirus (RRV). siRNA specific to NSP4 (siRNANSP4) significantly attenuated secretion of 5-HT compared to siRNAVP4, siRNAVP6 , siRNAVP7 and non-targeting (Nt) siRNAnt. Intracellular calcium clamping with BABTA/AM showed that intracellularly expressed NSP4-stimulated secretion of 5-HT from EC cells was calcium-dependent. Furthermore RV down-regulated the 5-HT transporter (SERT) mRNA in ileum but not tryptophan hydroxylase 1 (TPH1) mRNA the rate-limiting enzyme for 5-HT synthesis. The unaffected expression of TPH1 mRNA in the intestinal segments suggests that release of 5- HT primarily originates from pre-made 5-HT rather than from newly synthesised 5-HT mRNA. Moreover, down-regulation of SERT mRNA in ileum presumably resulted in reduced re- uptake of 5-HT by SERT to EC cells and thus increased extracellular 5-HT in the small intestine. Moreover, 7/7 infant mice responded following intraperitoneal administration of 5-HT with rapid (<30 min) diarrhoea in dose-dependent manner. In the light of these results and the fact that both 5-HT and NSP4 can induce diarrhoea in mice, a disease mechanism to RV diarrhoea is proposed.

National Category
Microbiology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-117893 (URN)
Available from: 2015-05-13 Created: 2015-05-13 Last updated: 2018-01-11Bibliographically approved
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