TY - JOUR
TI - Genetic contribution of MHC class II genes in susceptibility to west nile virus infection
AU - Sarri, C.A.
AU - Markantoni, M.
AU - Stamatis, C.
AU - Papa, A.
AU - Tsakris, A.
AU - Pervanidou, D.
AU - Baka, A.
AU - Politis, C.
AU - Billinis, C.
AU - Hadjichristodoulou, C.
AU - Mamuris, Z.
JO - PLOS ONE
PY - 2016
VL - 11
TODO - 11
SP - null
PB - Public Library of Science
SN - null
TODO - 10.1371/journal.pone.0165952
TODO - HLA DQA1 antigen;  HLA DRB1 antigen;  major histocompatibility antigen class 2;  HLA D antigen, Article;  central nervous system infection;  cohort analysis;  controlled study;  female;  Flavivirus infection;  gene;  gene frequency;  gene locus;  genetic association;  genetic susceptibility;  genotype;  Greek (people);  high risk population;  HLA DPA1 gene;  human;  infection risk;  infection sensitivity;  major clinical study;  male;  MHC class II gene;  phenotype;  population research;  risk assessment;  validation study;  West Nile virus;  case control study;  exon;  genetic polymorphism;  genetic predisposition;  genetics;  homozygote;  middle aged;  physiology;  West Nile fever;  West Nile virus, Case-Control Studies;  Exons;  Female;  Gene Frequency;  Genetic Predisposition to Disease;  HLA-D Antigens;  Homozygote;  Humans;  Male;  Middle Aged;  Polymorphism, Genetic;  West Nile Fever;  West Nile virus
TODO - WNV is a zoonotic neurotropic flavivirus that has recently emerged globally as a significant cause of viral encephalitis. The last five years, 624 incidents of WNV infection have been reported in Greece. The risk for severe WNV disease increases among immunosuppressed individuals implying thus the contribution of the MHC locus to the control of WNV infection. In order to investigate a possible association of MHC class II genes, especially HLA-DPA1, HLA-DQA1, HLA-DRB1, we examined 105 WNV patients, including 68 cases with neuroinvasive disease and 37 cases with mild clinical phenotype, collected during the period from 2010 to 2013, and 100 control individuals selected form the Greek population. Typing was performed for exon 2 for all three genes. DQA1∗01:01 was considered to be "protective" against WNV infection (25.4% vs 40.1%, P = 0.004) while DQA1∗01:02 was associated with increased susceptibility (48.0% vs 32.1%, P = 0.003). Protection against neuroinvasion was associated with the presence of DRB1∗11:02 (4.99% vs 0.0%, P = 0.018). DRB1∗16:02 was also absent from the control cohort (P = 0.016). Three additional population control groups were used in order to validate our results. No statistically significant association with the disease was found for HLA-DPA alleles. The results of the present study provide some evidence that MHC class II is involved in the response to WNV infection, outlining infection "susceptibility" and "CNS-high-risk" candidates. Furthermore, three new alleles were identified while the frequency of all alleles in the study was compared with worldwide data. The characterization of the MHC locus could help to estimate the risk for severe WNV cases in a country. © 2016 Sarri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ER -