Genetic Contribution of MHC Class II Genes in Susceptibility to West Nile Virus Infection.
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 to2013, 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.
Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Constantina A
CA
Sarri
Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Maria
M
Markantoni
Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Costas
C
Stamatis
Arboviruses Reference Laboratory, 1st Microbiological Laboratory, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Anna
A
Papa
Laboratory of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Athanasios
A
Tsakris
Hellenic Centre for Disease Control and Prevention (HCDCP), Attika, Greece.
Danai
D
Pervanidou
Hellenic Centre for Disease Control and Prevention (HCDCP), Attika, Greece.
Agoritsa
A
Baka
Hellenic coordinating Hemovigilance Center of HCDCP, Attika, Greece.
Constantina
C
Politis
Laboratory of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Thessaly, Karditsa, Greece.
Charalambos
C
Billinis
Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Christos
C
Hadjichristodoulou
Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Zissis
Z
Mamuris
D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014901:West Nile Fever / Q000235:genetics*; D014902:West Nile virus / Q000502:physiology*
D006681:HLA-D Antigens