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Genetic susceptibility to symptomatic norovirus infection in Nicaragua
Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
Department of Microbiology, University of León, Nicaragua.
Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
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2009 (English)In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 81, no 4, 728-735 p.Article 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. Vol. 81, no 4, 728-735 p.
Keyword [en]
secretors status; Lewis phenotype; blood groups; Norovirus genogroups
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-68384DOI: 10.1002/jmv.21426ISI: 000263765900022OAI: oai:DiVA.org:liu-68384DiVA: diva2:418440
Available from: 2011-05-23 Created: 2011-05-23 Last updated: 2017-12-11
In thesis
1. The Norovirus Puzzle: Characterization of human and bovine norovirus susceptibility patterns
Open this publication in new window or tab >>The Norovirus Puzzle: Characterization of human and bovine norovirus susceptibility patterns
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Winter vomiting disease is caused by norovirus (NoV) and affects millions of people every year resulting in 200.000 deaths among children in developing countries. It was observed early that not all individuals exposed to the norovirus became ill. The reason for this is now recognized to be dependent upon the secretor status of an individual. The secretor status determines the ability of an individual to express histo-blood group antigens (HBGA) on mucosa and in saliva. A non-secretor is unable to express HBGAs due to a mutation in a gene called FUT2. In this thesis, I have investigated the antibody prevalence and titer in humans in Sweden and Nicaragua to the most common GII NoV and the correlation to secretor status, Lewis status and ABO. I found that secretors had significantly higher antibody prevalence and titer to GII NoV than non-secretors suggesting that non-secretors are less prone to be infected by the GII NoV. In Nicaragua, I also found several different NoV strains circulating at the same time. The NoVs have been circulating and evolving in the human population for some time and the same individuals seems to be infected over and over again with the same virus. This suggests that there is no long-term immunity present but possibly short-term immunity, which would make it very difficult to produce a vaccine against NoV. However, recent studies have shown the possibility of using virus like particles as a vaccine candidate and have demonstrated long-term immunity.

The bovine NoV (boNoV) cause gastroenteritis in cattle and are closely related to the human NoV. The possibility of zoonotic transfer to humans is currently being investigated. I found that 26% of Swedish blood donors have antibodies to the boNoV suggesting that they have been exposed to the virus. The human NoV has been observed to be able to infect and cause disease in cattle, could the boNoV do the same in humans? To date, no boNoV strain has been found in humans. The proposed receptor structure for boNoV is the αGal epitope, which is present in many mammals like cow, pig, horse, sheep and rabbit but not in humans. This indicates that humans are not at risk for boNoV infection because we lack the proper receptor structure. However, recombinations between different NoV strains have been demonstrated and the possibility of more than one receptor being present has been suggested. I found that aa position 365-379 on the boNoV capsid seems to be important for binding to erythrocytes. In this thesis, I hope to add some new pieces to the Norovirus Puzzle.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1244
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-68386 (URN)978-91-7393-181-6 (ISBN)
Public defence
2011-05-20, Berzelius salen, ing. 65, Campus US, Linköpings universitet, Linköping, 13:00 (English)
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Available from: 2011-06-01 Created: 2011-05-23 Last updated: 2011-06-01Bibliographically approved

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Kindberg, ElinVildevall, MalinSvensson, Lennart

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