Association between the DQA MHC class II gene and Puumala virus infection in Myodes glareolus, the bank vole.

Puumala virus (PUUV) is a hantavirus specifically harboured by the bank vole, Myodes (earlier Clethrionomys) glareolus. It causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans, called Nephropathia epidemica (NE). The clinical severity of NE is variable among patients and depends on their major histocompatibility complex (MHC) genetic background. In this study we investigated the potential role of class II MHC gene polymorphism in the susceptibility/resistance to PUUV in the wild reservoir M. glareolus. We performed an association study between the exon 2 of the DQA gene and PUUV antibodies considering a natural population of bank voles. Because immune gene polymorphism is likely to be driven by multiple parasites in the wild, we also screened bank voles for other potential viral and parasitic infections. We used multivariate analyses to explore DQA polymorphism/PUUV associations while considering the potential antagonist and/or synergistic effects of the whole parasite community. Our study suggests links between class II MHC characteristics and viral infections including PUUV and Cowpox virus. Several alleles are likely to be involved in the susceptibility or in the resistance of bank voles to these infections. Alternatively, heterozygosity does not seem to be associated with PUUV or any other parasite infections. This result thus provides no evidence in favour of the hypothesis of selection through overdominance. Finally this multivariate approach reveals a strong antagonism between ectoparasitic mites and PUUV, suggesting direct or indirect immunogenetic links between infections by these parasites. Other datasets are now required to confirm these results and to test whether the associations vary in space and/or time.