title: Tnf-α expression and promoter sequences reflect the balance of tolerance/resistance to Puumala hantavirus infection in European bank vole populations.
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.
authors.affiliation: INRA, UMR CBGP (INRA/IRD/Cirad/Montpellier SupAgro), Campus International de Baillarguet, CS 30016, Montferrier-sur-Lez Cedex, France. guivier@supagro.inra.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Guivier
authors.forename: Maxime
authors.initials: M
authors.lastname: Galan
authors.forename: Alexis Ribas
authors.initials: AR
authors.lastname: Salvador
authors.forename: Anne
authors.initials: A
authors.lastname: Xuéreb
authors.forename: Yannick
authors.initials: Y
authors.lastname: Chaval
authors.forename: Gert E
authors.initials: GE
authors.lastname: Olsson
authors.forename: Sandra
authors.initials: S
authors.lastname: Essbauer
authors.forename: Heikki
authors.initials: H
authors.lastname: Henttonen
authors.forename: Liina
authors.initials: L
authors.lastname: Voutilainen
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cosson
authors.forename: Nathalie
authors.initials: N
authors.lastname: Charbonnel
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003411:Arvicolinae / Q000235:genetics* / Q000821:virology*; D001483:Base Sequence; D005060:Europe; D015870:Gene Expression; D005838:Genotype; D018778:Hantavirus Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D007113:Immunity, Innate; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D029262:Puumala virus / Q000276:immunology; D012376:Rodent Diseases / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D014409:Tumor Necrosis Factor-alpha