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Kindberg, Elin
Alternative names
Publications (10 of 14) Show all publications
Kindberg, E., Vene, S., Mickiene, A., Lundkvist, A., Lindquist, L. & Svensson, L. (2011). A Functional Toll-Like Receptor 3 Gene (TLR3) May Be a Risk Factor for Tick-borne Encephalitis Virus (TBEV) Infection. JOURNAL OF INFECTIOUS DISEASES, 203(4), 523-528
Open this publication in new window or tab >>A Functional Toll-Like Receptor 3 Gene (TLR3) May Be a Risk Factor for Tick-borne Encephalitis Virus (TBEV) Infection
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2011 (English)In: JOURNAL OF INFECTIOUS DISEASES, ISSN 0022-1899, Vol. 203, no 4, p. 523-528Article in journal (Refereed) Published
Abstract [en]

Background. Tick-borne encephalitis virus (TBEV) infections may be asymptomatic or cause severe symptoms in the central nervous system. A mutation in the chemokine receptor 5 gene has been associated with increased risk of TBE but explains only a limited number of cases. Investigations of further risk factors are needed. Method. To investigate the importance of the innate immune response, we analyzed 128 TBE patients, 77 patients with aseptic meningoencephalitis (AME) and 135 healthy controls, for 3mutations: 2 in the Toll-like receptor 3 (TLR3) gene and 1 in the 2-5-oligoadenylate synthetase (OAS1) gene. Results. Although no association was found between the mutation in the OAS1 gene and TBE, the genotype distribution ofrs3775291, a mutation in TLR3, differed significantly between TBE patients and controls; 61%, 32%, and 7% of the TBE patients were carriers of the wild-type, heterozygous, and mutant genotype of rs3775291, respectively. The corresponding percentages among healthy controls (n = 126) were 52%, 29%, and 19% (P = .02), and among AME patients (n = 75) were 47%, 32%, and 21% (P = .009). Additionally, the wild-type rs3775291 allele was more common among TBE patients than among healthy controls (allele frequency, .768 vs .663; P = .01). Conclusion. A functional TLR3 is a risk factor for TBEV infection.

Place, publisher, year, edition, pages
University of Chicago Press, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-65716 (URN)10.1093/infdis/jiq082 (DOI)000286468700013 ()
Available from: 2011-02-18 Created: 2011-02-18 Last updated: 2011-02-18
Rydell, G. E., Kindberg, E., Larson, G. & Svensson, L. (2011). Susceptibility to winter vomiting disease: a sweet matter. Reviews in Medical Virology, 21(6), 370-382
Open this publication in new window or tab >>Susceptibility to winter vomiting disease: a sweet matter
2011 (English)In: Reviews in Medical Virology, ISSN 1052-9276, E-ISSN 1099-1654, Vol. 21, no 6, p. 370-382Article, review/survey (Refereed) Published
Abstract [en]

Norovirus, the cause of winter vomiting disease, has emerged in recent years to be a major cause of sporadic and epidemic gastroenteritis worldwide. The virus has been estimated to cause andgt;200 000 deaths each year in developing countries. Although the virus is highly contagious, volunteer and field studies have shown that a subset of individuals appears resistant to infections. A single nucleotide mutation (G428A) in the fucosyltransferase gene (FUT2) on chromosome 19 provides strong protection from infection in 20% of the white population. Histo-blood group ABO(H) antigens with terminal fucose are believed to function as receptors for human norovirus in the gastrointestinal tract, but also negatively charged potential receptors have been identified. Norovirus infection is a unique example where a single nucleotide mutation in a fucosyltransferase gene plays a crucial role in susceptibility to one of the most common viral diseases. This review discusses the role of host genetics and carbohydrate structures in susceptibility to winter vomiting disease.

Place, publisher, year, edition, pages
John Wiley and Sons, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72820 (URN)10.1002/rmv.704 (DOI)000296904500005 ()
Note
Funding Agencies|Swedish Research Council|1039282662010-878|Available from: 2011-12-08 Created: 2011-12-08 Last updated: 2017-12-08
Kindberg, E. (2010). Host genetic risk factors to viral diseases - a double-edged sword: Studies of norovirus and tick-borne encephalitis virus. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Host genetic risk factors to viral diseases - a double-edged sword: Studies of norovirus and tick-borne encephalitis virus
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It is today well known that the outcome of a certain infection depends on factors of both the host and the pathogen. Studies of host genetic susceptibility to infectious diseases aim to increase the understanding of why some individuals are more susceptible than others, to a certain infection. Knowledge of genetic susceptibility to a viral disease may be used in development of new therapeutic means, and also to recognize individuals who are at increased risk of severe symptoms if infected with a pathogen. It seems however that a risk factor for one disease may play a protective role in another situation; like a double-edged sword.

In this thesis I have studied genetic factors affecting susceptibility to norovirus (NoV) and factors affecting the risk of developing tick-borne encephalitis (TBE) after infection with TBE virus (TBEV). NoV is the cause of the “winter vomiting disease”, affecting millions of people every year, and causing up to 200,000 fatalities among children in developing countries, each year. It is today recognized that the secretor status of an individual, i.e. the ability to express ABO blood groups and related antigens, in secretions and on mucosa, affect the risk of being infected by NoV. By studying authentic NoV outbreaks in Denmark, Spain and Sweden and by comparing the secretor status of affected and unaffected individuals we were able to confirm that secretor status have indeed great impact on susceptibility to some NoV strains, but also that there are strains circulating, which infect individuals regardless of secretor status.

TBEV is endemic in many parts of Europe and Asia but studies have shown that 70-95% of all infections are asymptomatic or sub-clinical. Some individuals do however develop TBE, a severe disease including meningitis or encephalitis with or without myelitis. Also, many patients suffer from long-time sequelae and TBEV infections may in worst case be fatal. The reason for difference in disease outcome is not known and we have chosen to study if genetic factors affecting the immune response may play a role in disease outcome. To do this we used a prospectively collected Lithuanian material with samples from patients with TBE, AME (aseptic meningoencephalitis) and matched healthy controls. So far we have found that a deletion in chemokine receptor 5 (CCR5), a gene encoding a receptor involved in cell migration, is a risk factor for developing disease. We have also data showing that toll-like receptor 3 (TLR3), a receptor recognizing double stranded RNA (dsRNA), which is a product of TBEV replication, may instead of being protective increase the risk of TBE.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. p. 77
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1183
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-54923 (URN)978-91-7393-393-3 (ISBN)
Public defence
2010-05-28, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2010-04-27 Created: 2010-04-22 Last updated: 2018-01-12Bibliographically approved
Nordgren, J., Kindberg, E., Lindgren, P.-E., Matussek, A. & Svensson, L. (2009). A FUT2 nonsense mutation (G428A) and Lewis-independent norovirus GI.3 outbreak.
Open this publication in new window or tab >>A FUT2 nonsense mutation (G428A) and Lewis-independent norovirus GI.3 outbreak
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2009 (English)Article in journal (Other academic) Submitted
Abstract [en]

Background: Norovirus (NoV) is recognized as the commonest cause of acute gastroenteritis among adults. Previous studies have shown that histo-blood group antigens (HBGAs) and secretor status are associated with susceptibility to symptomatic NoV infection, with non-secretors being almost completely resistant to disease. Here we report on a food-borne GI.3 NoV outbreak affecting 33/83 (40%) individuals.

Methods: Secretor status and HBGA expression in saliva were determined with pyrosequencing and ELISA. Virus characterization was performed by sequencing the N/S region and the complete capsid gene.

Results: A novel observation was that homozygous carriers of the nonsense FUT2 G428A allele were more susceptible to symptomatic infection than secretors (odds ratio [OR] 1.41 vs 0.71). Consistent with this observation was that Lewis a positive b negative (Lea+b-) individuals showed the highest susceptibility (OR 2.42) compared with other Lewis phenotypes. Blood group B was associated with partial protection (OR 0.27). The capsid gene of the outbreak strain exhibits high amino acid homology with the Kashiwa645 GI.3 strain, previously shown to recognize non-secretor saliva.

Conclusion: We describe for the first time a NoV outbreak with Lea+b- individuals homozygous for the G428A nonsense mutation in the FUT2 gene being more susceptible for disease than secretor-positive individuals.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17686 (URN)
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2009-04-14Bibliographically approved
Kindberg, E., Ax, C., Fiore, L. & Svensson , L. (2009). Ala67Thr Mutation in the Poliovirus Receptor CD155 is a Potential Risk Factor for Vaccine and Wild-Type Paralytic Poliomyelitis. JOURNAL OF MEDICAL VIROLOGY, 81(5), 933-936
Open this publication in new window or tab >>Ala67Thr Mutation in the Poliovirus Receptor CD155 is a Potential Risk Factor for Vaccine and Wild-Type Paralytic Poliomyelitis
2009 (English)In: JOURNAL OF MEDICAL VIROLOGY, ISSN 0146-6615 , Vol. 81, no 5, p. 933-936Article in journal (Refereed) Published
Abstract [en]

Poliovirus infections can be asymptomatic or cause severe paralysis. Why some individuals develop paralytic poliomyelitis is unknown, but a role for host genetic factors has been suggested. To investigate if a polymorphism, Ala67Thr, in the poliovirus receptor, which has been found to facilitate increased resistance against poliovirus-induced cell lysis and apoptosis, is associated with increased risk of paralytic poliomyelitis, poliovirus receptor genotyping was undertaken among Italian subjects with vaccine-associated (n = 9), or with wild-type paralytic poliomyelitis (n = 6), and control subjects (n = 71), using RFLP-PCR and pyrosequencing. Heterozygous poliovirus receptor Ala67Thr genotype was found in 13.3% of the patients with paresis and in 8.5% of the controls (Odds Ratio = 1.667). The frequency of Ala67Thr among the controls is in agreement with earlier published data. It is concluded that the Ala67Thr mutation in the poliovirus receptor is a possible risk factor for the development of vaccine-associated or paralytic poliomyelitis associated with wild-type virus.

Keywords
poliovirus, poliovirus receptor, paralytic poliomyelitis, vaccine-associated paralytic poliomyelitis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17890 (URN)10.1002/jmv.21444 (DOI)
Available from: 2009-04-26 Created: 2009-04-24 Last updated: 2009-04-26
Kindberg, E. & Svensson, L. (2009). Genetic basis of host resistance to norovirus infection. FUTURE VIROLOGY, 4(4), 369-382
Open this publication in new window or tab >>Genetic basis of host resistance to norovirus infection
2009 (English)In: FUTURE VIROLOGY, ISSN 1746-0794, Vol. 4, no 4, p. 369-382Article, review/survey (Refereed) Published
Abstract [en]

Noroviruses have emerged as a major cause of acute gastroenteritis in humans of all ages and are responsible for 200,000 deaths every year, mainly in developing countries. Despite high infectivity and lack of long-term immunity, authentic and volunteer studies have shown existence of inherited protective factors. Recent studies have shown that secretor status controlled by the alpha(1,2)-fucosyltransferase gene located on chromosome 19 determines susceptibility to most, if not all, norovirus infections, with individuals homozygous for the G428A nonsense mutation (nonsecretors) representing 20% of the highly protected European population.

Keywords
gastroenteritis; histo-blood group antigens; host genetics; norovirus; secretor status; susceptibility; viral evolution
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-20140 (URN)10.2217/fvl.09.14 (DOI)000268120000012 ()
Available from: 2009-08-31 Created: 2009-08-31 Last updated: 2018-01-13
Bucardo, F., Kindberg, E., Paniagua, M., Vildevall, M. & Svensson, L. (2009). Genetic susceptibility to symptomatic norovirus infection in Nicaragua. Journal of Medical Virology, 81(4), 728-735
Open this publication in new window or tab >>Genetic susceptibility to symptomatic norovirus infection in Nicaragua
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2009 (English)In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 81, no 4, p. 728-735Article in journal (Refereed) Published
Abstract [en]

Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.

Place, publisher, year, edition, pages
John Wiley & Sons, 2009
Keywords
secretors status; Lewis phenotype; blood groups; Norovirus genogroups
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-68384 (URN)10.1002/jmv.21426 (DOI)000263765900022 ()
Available from: 2011-05-23 Created: 2011-05-23 Last updated: 2018-01-12
Carlsson, B., Kindberg, E., Buesa, J., Rydell, G. E., Lidón, M. F., Montava, R., . . . Svensson, L. (2009). The G428A nonsense mutation in FUT2 provides strong but not absolute protection against symptomatic GII.4 Norovirus infection.. PLoS ONE, 4(5), e5593
Open this publication in new window or tab >>The G428A nonsense mutation in FUT2 provides strong but not absolute protection against symptomatic GII.4 Norovirus infection.
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2009 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 5, p. e5593-Article in journal (Refereed) Published
Abstract [en]

In November 2004, 116 individuals in an elderly nursing home in El Grao de Castellón, Spain were symptomatically infected with genogroup II.4 (GII.4) norovirus. The global attack rate was 54.2%. Genotyping of 34 symptomatic individuals regarding the FUT2 gene revealed that one patient was, surprisingly, a non-secretor, hence indicating secretor-independent infection. Lewis genotyping revealed that Lewis-positive and negative individuals were susceptible to symptomatic norovirus infection indicating that Lewis status did not predict susceptibility. Saliva based ELISA assays were used to determine binding of the outbreak virus to saliva samples. Saliva from a secretor-negative individual bound the authentic outbreak GII.4 Valencia/2004/Es virus, but did not in contrast to secretor-positive saliva bind VLP of other strains including the GII.4 Dijon strain. Amino acid comparison of antigenic A and B sites located on the external loops of the P2 domain revealed distinct differences between the Valencia/2004/Es and Dijon strains. All three aa in each antigenic site as well as 10/11 recently identified evolutionary hot spots, were unique in the Valencia/2004/Es strain compared to the Dijon strain. To the best of our knowledge, this is the first example of symptomatic GII.4 norovirus infection of a Le(a+b-) individual homozygous for the G428A nonsense mutation in FUT2. Taken together, our study provides new insights into the host genetic susceptibility to norovirus infections and evolution of the globally dominating GII.4 viruses.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18974 (URN)10.1371/journal.pone.0005593 (DOI)19440360 (PubMedID)
Note
Original Publication: Beatrice Carlsson, Elin Kindberg, Javier Buesa, Gustaf E Rydell, Marta Fos Lidón, Rebeca Montava, Reem Abu Mallouh, Ammi Grahn, Jesús Rodríguez-Díaz, Juan Bellido, Alberto Arnedo, Göran Larson and Lennart Svensson, The G428A nonsense mutation in FUT2 provides strong but not absolute protection against symptomatic GII.4 Norovirus infection., 2009, PLoS ONE, (4), 5, e5593. http://dx.doi.org/10.1371/journal.pone.0005593 Licensed under Creative CommonsAvailable from: 2009-06-10 Created: 2009-06-07 Last updated: 2017-12-13Bibliographically approved
Kindberg, E., Mickiene, A., Ax, C., Åkerlind, B., Vene, S., Lindquist, L., . . . Svensson, L. (2008). A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis. Journal of Infectious Diseases, 197(2), 266-269
Open this publication in new window or tab >>A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis
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2008 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 197, no 2, p. 266-269Article in journal (Refereed) Published
Abstract [en]

Tickborne encephalitis (TBE) virus infections can be asymptomatic or cause moderate to severe injuries of the central nervous system. Why some individuals develop severe disease is unknown, but a role for host genetic factors has been suggested. To investigate whether chemokine receptor CCR5 is associated with TBE, CCR5Δ32 genotyping was performed among Lithuanian patients with TBE (n = 129) or with aseptic meningoencephalitis (n = 76) as well as among control subjects (n = 134). We found individuals homozygous for CCR5Δ32 (P = .026) only among patients with TBE and a higher allele prevalence among patients with TBE compared with the other groups studied. CCR5Δ32 allele prevalence also increased with the clinical severity of disease. © 2007 by the Infectious Diseases Society of America. All rights reserved.

Keywords
Alleles Encephalitis, Tick-Borne/epidemiology/*genetics/physiopathology *Gene Deletion Gene Frequency *Genetic Predisposition to Disease Homozygote Humans Lithuania/epidemiology Meningoencephalitis/genetics Receptors, CCR5/*genetics Severity of Illness In
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-43369 (URN)10.1086/524709 (DOI)73655 (Local ID)73655 (Archive number)73655 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
Kindberg, E., Åkerlind, B., Johnsen, C., Knudsen, J. D., Heltberg, O., Larson, G., . . . Svensson, L. (2007). Host genetic resistance to symptomatic norovirus (GGII.4) infections in Denmark. Journal of Clinical Microbiology, 45(8), 2720-2722
Open this publication in new window or tab >>Host genetic resistance to symptomatic norovirus (GGII.4) infections in Denmark
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2007 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 45, no 8, p. 2720-2722Article in journal (Refereed) Published
Abstract [en]

A total of 61 individuals involved in five norovirus outbreaks in Denmark were genotyped at nucleotides 428 and 571 of the FUT2 gene, determining secretor status, i.e., the presence of ABH antigens in secretions and on mucosa. A strong correlation (P = 0.003) was found between the secretor phenotype and symptomatic disease, extending previous knowledge and confirming that nonsense mutations in the FUT2 gene provide protection against symptomatic norovirus (GGII.4) infections. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-40699 (URN)10.1128/JCM.00162-07 (DOI)53918 (Local ID)53918 (Archive number)53918 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
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