Abstract
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.
Highlights
West Nile Virus (WNV) is a zoonotic neurotropic arbovirus of the Flaviviridae family that has recently emerged globally as a significant cause of viral encephalitis [1]
The major histocompatibility complex (MHC) class I polymorphism has been associated with the outcome of WNV infection; in an American cohort study, HLA-BÃ40 and CÃ03 were attributed a protective role contrary to HLA-AÃ68 and CÃ08 that were associated with the development of neurological symptoms [12]
The present study offers valuable insight regarding the possible influence of the MHC class II background in the infection and outcome of the WNV disease
Summary
West Nile Virus (WNV) is a zoonotic neurotropic arbovirus of the Flaviviridae family that has recently emerged globally as a significant cause of viral encephalitis [1]. The high proportion of neuroinvasive cases, which is not a WNV-disease characteristic, reflects the majority of unreported subclinical or asymptomatic infections. The risk for developing a more severe form of WNV disease increases among immunosuppressed individuals and organ transplant recipients [5], the elderly [6, 7] and men [8]. Immunosuppression due to defective CD4+ and CD8+ T-cell response was shown to contribute to WNV infection of the Central Nervous System (CNS) and increased mortality rates [9,10,11]. The contribution of HLA-A locus to the development of immune responses that control WNV infection was recently supported by mass spectroscopy data [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
