Numerical model for in-vitro ultrasound stimulation of bone cells: a parametric study

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Landscape genetics highlights the role of bank vole metapopulation dynamics in the epidemiology of Puumala hantavirus

Rodent host dynamics and dispersal are thought to be critical for hantavirus epidemiology as they determine pathogen persistence and transmission within and between host populations. We used landscape genetics to investigate how the population dynamics of the bank vole Myodes glareolus, the host of Puumala hantavirus (PUUV), vary with forest fragmentation and influence PUUV epidemiology. We sampled vole populations within the Ardennes, a French PUUV endemic area. We inferred demographic features such as population size, isolation and migration with regard to landscape configuration. We next analysed the influence of M. glareolus population dynamics on PUUV spatial distribution. Our results revealed that the global metapopulation dynamics of bank voles were strongly shaped by landscape features, including suitable patch size and connectivity. Large effective size in forest might therefore contribute to the higher observed levels of PUUV prevalence. By contrast, populations from hedge networks highly suffered from genetic drift and appeared strongly isolated from all other populations. This might result in high probabilities of local extinction for both M. glareolus and PUUV. Besides we detected signatures of asymmetric bank vole migration from forests to hedges. These movements were likely to sustain PUUV in fragmented landscapes. In conclusion, our study provided arguments in favour of source-sink dynamics shaping PUUV persistence and spread in heterogeneous, western European temperate landscapes. It illustrated the potential contribution of landscape genetics to the understanding of the epidemiological processes occurring at this local scale

Tnf-alpha expression and promoter sequences reflect the balance of tolerance/resistance to Puumala hantavirus infection in European bank vole populations

International audienceThe tumor necrosis factor-alpha (TNF-alpha) influences the ability to limit parasite infection but its over-production might result in inflammatory disorders. The level of Tnf-alpha 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-alpha. 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-alpha. We investigated the hypothesis that bank voles from PUUV endemic areas should exhibit higher levels of tolerance, i.e. lower levels of TNF-alpha production, than bank voles from areas where PUUV prevalence is low. For this purpose, we analysed variations of Tnf-alpha gene expression and promoter sequences among European populations of bank voles. Our results revealed an absence of up-regulation of Tnf-alpha gene expression in PUUV infected bank voles and significant differences in Tnf-alpha 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-alpha promoter (-302 GG/GG and -296 A/A) were associated with higher Tnf-alpha gene expression and were more frequent in non-endemic areas. This study emphasized the potential influence of selection acting on TNF-alpha 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-alpha expression levels, should provide important keys to understand the prevalence of PUUV over Europe

Associations between MHC genes and Puumala virus infection in Myodes glareolus are detected in wild populations, but not from experimental infection data

Correspondence Nathalie Charbonnel nathalie.charbonnel@supagro. inra.frInternational audienceWe analysed the influence of MHC class II Dqa and Drb genes on Puumala virus (PUUV) infection in bank voles (Myodes glareolus). We considered voles sampled in five European localities or derived from a previous experiment that showed variable infection success of PUUV The genetic variation observed in the Dqa and Drb genes was assessed by using single-strand conformation polymorphism and pyrosequencing methods, respectively. Patterns were compared with those obtained from 13 microsatellites. We revealed significant genetic differentiation between PUUV-seronegative and -seropositive bank voles sampled in wild populations, at the Drb gene only The absence of genetic differentiation observed at neutral microsatellites confirmed the important role of selective pressures in shaping these Drb patterns Also, we found no significant associations between infection success and MHC alleles among laboratory-colonized bank voles, which is explained by a loss of genetic variability that occurred during the captivity of these vole

Landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for Puumala virus epidemiology.

Heterogeneity in environmental conditions helps to maintain genetic and phenotypic diversity in ecosystems. As such, it may explain why the capacity of animals to mount immune responses is highly variable. The quality of habitat patches, in terms of resources, parasitism, predation and habitat fragmentation may, for example, trigger trade-offs ultimately affecting the investment of individuals in various immunological pathways. We described spatial immunoheterogeneity in bank vole populations with respect to landscape features and co-infection. We focused on the consequences of this heterogeneity for the risk of Puumala hantavirus (PUUV) infection. We assessed the expression of the Tnf-α and Mx2 genes and demonstrated a negative correlation between PUUV load and the expression of these immune genes in bank voles. Habitat heterogeneity was partly associated with differences in the expression of these genes. Levels of Mx2 were lower in large forests than in fragmented forests, possibly due to differences in parasite communities. We previously highlighted the positive association between infection with Heligmosomum mixtum and infection with PUUV. We found that Tnf-α was more strongly expressed in voles infected with PUUV than in uninfected voles or in voles co-infected with the nematode H. mixtum and PUUV. H. mixtum may limit the capacity of the vole to develop proinflammatory responses. This effect may increase the risk of PUUV infection and replication in host cells. Overall, our results suggest that close interactions between landscape features, co-infection and immune gene expression may shape PUUV epidemiology