Host genetic risk factors for West Nile virus infection and disease progression
AuthorsBigham, Abigail W.
Buckingham, Kati J.
Edmond, Mary J.
Bofferding, Kathryn M.
Astakhova, Natalia M.
Perelygin, Andrey A.
Busch, Michael P.
Murray, Kristy O.
Sejvar, James J.
Brinton, Margo A.
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
Genetic Predisposition to Disease
Interferon Regulatory Factor-3
Polymorphism, Single Nucleotide
West Nile Fever
Medicine and Health Sciences
MetadataShow full item record
AbstractWest Nile virus (WNV), a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035) and MX1, (OR 0.19, p = 0.014) were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003) was associated with increased risk for West Nile encephalitis and paralysis (WNE/P). Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.
PLoS One. 2011;6(9):e24745. Epub 2011 Sep 15. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/50985
RightsThis is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.