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Identifying factors that drive infection dynamics in reservoir host populations is essential in understanding human risk from wildlife-originated zoonoses. We studied zoonotic Puumala orthohantavirus (PUUV) in the host, the bank vole (Myodes glareolus), populations in relation to the host population, rodent and predator community and environment-related factors and whether these processes are translated into human infection incidence. We used 5-year rodent trapping and bank vole PUUV serology data collected from 30 sites located in 24 municipalities in Finland. We found that PUUV seroprevalence in the host was negatively associated with the abundance of red foxes, but this process did not translate into human disease incidence, which showed no association with PUUV seroprevalence. The abundance of weasels, the proportion of juvenile bank voles in the host populations and rodent species diversity were negatively associated with the abundance index of PUUV positive bank voles, which, in turn, showed a positive association with human disease incidence. Our results suggest certain predators, a high proportion of young bank vole individuals, and a diverse rodent community, may reduce PUUV risk for humans through their negative impacts on the abundance of infected bank voles. [ABSTRACT FROM AUTHOR]

Intensive management of Fennoscandian forests has led to a mosaic of woodlands in different stages of maturity. The main rodent host of the zoonotic Puumala hantavirus (PUUV) is the bank vole (Myodes glareolus), a species that can be found in all woodlands and especially mature forests. We investigated the influence of forest age structure on PUUV infection dynamics in bank voles. Over four years, we trapped small mammals twice a year in a forest network of different succession stages in Northern Finland. Our study sites represented four forest age classes from young (4 to 30 years) to mature (over 100 years) forests. We show that PUUV-infected bank voles occurred commonly in all forest age classes, but peaked in mature forests. The probability of an individual bank vole to be PUUV infected was positively related to concurrent host population density. However, when population density was controlled for, a relatively higher infection rate was observed in voles trapped in younger forests. Furthermore, we found evidence of a ''dilution effect'' in that the infection probability was negatively associated with the simultaneous density of other small mammals during the breeding season. Our results suggest that younger forests created by intensive management can reduce hantaviral load in the environment, but PUUV is common in woodlands of all ages. As such, the Fennoscandian forest landscape represents a significant reservoir and source of hantaviral infection in humans. [ABSTRACT FROM AUTHOR]

The influence of pathogens on host fitness is one of the key questions in infection ecology. Hantaviruses have coevolved with their hosts and are generally thought to have little or no effect on host survival or reproduction. We examined the effect of Puumala virus (PUUV) infection on the winter survival of bank voles (Myodes glareolus), the host of this virus. The data were collected by monitoring 22 islands over three consecutive winters (a total of 55 island populations) in an endemic area of central Finland. We show that PUUV infected bank voles had a significantly lower overwinter survival probability than antibody negative bank voles. Antibody negative female bank voles from low-density populations living on large islands had the highest survival. The results were similar at the population level as the spring population size and density were negatively correlated with PUUV prevalence in the autumn. Our results provide the first evidence for a significant effect of PUUV on host survival suggesting that hantaviruses, and endemic pathogens in general, deserve even more attention in studies of host population dynamics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: The tumor necrosis factor-alpha (TNF-α) influences the ability to limit parasite infection but its over-production might result in inflammatory disorders. The level of Tnf-α gene expression could thus mediate a balance of tolerance/resistance to infections. This study focused on Puumala hantavirus (PUUV) infection in its rodent host, the bank vole (Myodes glareolus). In humans, PUUV is responsible of a mild form of hemorrhagic fever with renal syndrome, nephropathia epidemica (NE). The severity of NE is associated with an over-production of TNF-α. By contrast, PUUV infection in bank vole is chronic and asymptomatic. It is likely that different coevolutionary histories between PUUV and its hosts could lead to different balances of resistance/tolerance to PUUV infection, at least partly mediated by variable production levels of TNF-α. We investigated the hypothesis that bank voles from PUUV endemic areas should exhibit higher levels of tolerance, i.e. lower levels of TNF-α production, than bank voles from areas where PUUV prevalence is low. For this purpose, we analysed variations of Tnf-α gene expression and promoter sequences among European populations of bank voles. Our results revealed an absence of up-regulation of Tnf-α gene expression in PUUV infected bank voles and significant differences in Tnf-α gene expression level with regard to PUUV endemicity. These results corroborated the hypothesis of different balances of tolerance/resistance to PUUV. Two single-nucleotide polymorphism genotypes within the Tnf-α promoter (−302 GG/GG and −296 A/A) were associated with higher Tnf-α gene expression and were more frequent in non-endemic areas. This study emphasized the potential influence of selection acting on TNF-α production and mediating a tolerance/resistance balance to PUUV in bank voles. Further investigations, including the role of phenotypic plasticity and parasite communities on Tnf-α expression levels, should provide important keys to understand the prevalence of PUUV over Europe. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]