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

• DOI: 10.1016/j.meegid.2010.07.022
• Publication Date: 2010-08-06T09:01:43Z
• Authors: Emmanuel Guivier; Maxime Galan; Alexis Ribas Salv...; Anne Xuéreb; Yannick Chaval; Gert E. Olsson; Sandra Essbauer; Heikki Henttonen; Liina Voutilainen; Jean-François Cosson; Nathalie Charbonnel
• Keywords: 0301 basic medicine; 570; Nephropathia epidemica; Genotype; Puumala hantavirus; [SDV]Life Sciences [q-bio]; Hantavirus Infections; Resistance; Gene Expression; Immunopathology; Antibodies, Viral; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Puumala virus; Rodent Diseases; 03 medical and health sciences; 616; Myodes glareolus; Tumor necrosis factor-alpha; Animals; Promoter Regions, Genetic; Reservoir; Base Sequence; Arvicolinae; Tumor Necrosis Factor-alpha; Immunity, Innate; 3. Good health; Europe; Tolerance

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.