Open AccessAssociation between HLA Class I and Class II Alleles and the Outcome of West Nile Virus Infection: An Exploratory Study
Author(s) -
Marion C. Lanteri,
Zhanna Kaidarova,
Trevor Peterson,
Steven Cate,
Brian Custer,
Shiquan Wu,
Maria Agapova,
Jacqueline Law,
Thomas Bielawny,
Frank Plummer,
Leslie H. Tobler,
Mark Loeb,
Michael P. Busch,
Jonathan L. Bramson,
Ma Luo,
Philip J. Norris
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0022948
Subject(s) - asymptomatic , allele , human leukocyte antigen , medicine , immunology , population , allele frequency , virology , biology , genetics , antigen , environmental health , gene
Background West Nile virus (WNV) infection is asymptomatic in most individuals, with a minority developing symptoms ranging from WNV fever to serious neuroinvasive disease. This study investigated the impact of host HLA on the outcome of WNV disease. Methods A cohort of 210 non-Hispanic mostly white WNV + subjects from Canada and the U.S. were typed for HLA-A, B, C, DP, DQ, and DR. The study subjects were divided into three WNV infection outcome groups: asymptomatic (AS), symptomatic (S), and neuroinvasive disease (ND). Allele frequency distribution was compared pair-wise between the AS, S, and ND groups using χ2 and Fisher's exact tests and P values were corrected for multiple comparisons ( Pc ). Allele frequencies were compared between the groups and the North American population (NA) used as a control group. Logistic regression analysis was used to evaluate the potential synergistic effect of age and HLA allele phenotype on disease outcome. Results The alleles HLA-A*68, C*08 and DQB*05 were more frequently associated with severe outcomes (ND vs. AS, P A*68 = 0.013/ Pc = 0.26, P C*08 = 0.0075/ Pc = 0.064, and P DQB1*05 = 0.029/ Pc = 0.68), However the apparent DQB1*05 association was driven by age. The alleles HLA-B*40 and C*03 were more frequently associated with asymptomatic outcome (AS vs. S, P B*40 = 0.021/ Pc = 0.58 and AS vs. ND P C*03 = 0.039/ Pc = 0.64) and their frequencies were lower within WNV + subjects with neuroinvasive disease than within the North American population (NA vs . S, P B*40 = 0.029 and NA vs. ND, P C*03 = 0.032). Conclusions Host HLA may be associated with the outcome of WNV disease; HLA-A*68 and C*08 might function as “susceptible” alleles, whereas HLA-B*40 and C*03 might function as “protective” alleles.