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Research article - Peer-reviewed, 2010

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

Guivier, E; Maxime Galan, M; Salvador, AR; Xuéreb, A; Chaval, Y; Olsson, Gert; Essbauer, S; Henttonen, H; Voutilainen, L; Cosson, J-F; Charbonnel, N


The 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. (C) 2010 Elsevier B.V. All rights reserved.


Myodes glareolus; Puumala hantavirus; Tumor necrosis factor-alpha; Nephropathia epidemica; Tolerance; Resistance; Immunopathology; Reservoir

Published in

Infection, Genetics and Evolution
2010, Volume: 10, number: 8, pages: 1208-1217

    UKÄ Subject classification

    Environmental Sciences related to Agriculture and Land-use

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