Experimental infections of wild bank voles (Myodes glareolus) from nephropatia epidemica endemic and non-endemic regions revealed slight differences in Puumala virological course and immunological responses.

In Europe, the occurrence of nephropathia epidemica (NE), a human disease caused by Puumala virus (PUUV), exhibits considerable geographical heterogeneity despite the continuous distribution of its reservoir, the bank vole Myodes glareolus. To better understand the causes of this heterogeneity, wild voles sampled in two adjacent NE endemic and non-endemic regions of France were infected experimentally with PUUV. The responses of bank voles to PUUV infection, based on the levels of anti-PUUV IgG and viral RNA, were compared. Slight regional differences were highlighted despite the high inter-individual variability. Voles from the NE non-endemic region showed greater immune responsiveness to PUUV infection, but lower levels of RNA in their organs than voles from the endemic region. These results suggest the existence of regional variations in the sensitivity of bank voles that could contribute to the apparent absence of PUUV circulation among voles and the absence of NE in the non-endemic region.

Microevolution of bank voles (Myodes glareolus) at neutral and immune-related genes during multiannual dynamic cycles: Consequences for Puumala hantavirus epidemiology.

Understanding how host dynamics, including variations of population size and dispersal, may affect the epidemiology of infectious diseases through ecological and evolutionary processes is an active research area. Here we focus on a bank vole (Myodes glareolus) metapopulation surveyed in Finland between 2005 and 2009. Bank vole is the reservoir of Puumala hantavirus (PUUV), the agent of nephropathia epidemica (NE, a mild form of hemorrhagic fever with renal symptom) in humans. M. glareolus populations experience multiannual density fluctuations that may influence the level of genetic diversity maintained in bank voles, PUUV prevalence and NE occurrence. We examine bank vole metapopulation genetics at presumably neutral markers and immune-related genes involved in susceptibility to PUUV (Tnf-promoter, Tlr4, Tlr7 and Mx2 gene) to investigate the links between population dynamics, microevolutionary processes and PUUV epidemiology. We show that genetic drift slightly and transiently affects neutral and adaptive genetic variability within the metapopulation. Gene flow seems to counterbalance its effects during the multiannual density fluctuations. The low abundance phase may therefore be too short to impact genetic variation in the host, and consequently viral genetic diversity. Environmental heterogeneity does not seem to affect vole gene flow, which might explain the absence of spatial structure previously detected in PUUV in this area. Besides, our results suggest the role of vole dispersal on PUUV circulation through sex-specific and density-dependent movements. We find little evidence of selection acting on immune-related genes within this metapopulation. Footprint of positive selection is detected at Tlr-4 gene in 2008 only. We observe marginally significant associations between Mx2 genotype and PUUV genogroups. These results show that neutral processes seem to be the main factors affecting the evolution of these immune-related genes at a contemporary scale, although the relative effects of neutral and adaptive forces could vary temporally with density fluctuations. Immune related gene polymorphism may in turn partly influence PUUV epidemiology in this metapopulation.