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Species-Specific Contribution of the Four C-Terminal Amino Acids of Influenza A Virus NS1 Protein to Virulence

Soubiès, Sébastien and Volmer, Christelle and Croville, Guillaume and Loupias, Josiane and Peralta, Brigitte and Costes, Pierrette and Lacroux, Caroline and Guérin, Jean-Luc and Volmer, Romain Species-Specific Contribution of the Four C-Terminal Amino Acids of Influenza A Virus NS1 Protein to Virulence. (2010) Journal of Virology, vol. 84 (13). pp. 6733-6747. ISSN 0022-538X

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Official URL: http://dx.doi.org/10.1128/JVI.02427-09

Abstract

Large-scale sequence analyses of influenza viruses revealed that nonstructural 1 (NS1) proteins from avian influenza viruses have a conserved C-terminal ESEV amino acid motif, while NS1 proteins from typical human influenza viruses have a C-terminal RSKV motif. To test the influence of the C-terminal domains of NS1 on the virulence of an avian influenza virus, we generated a wild-type H7N1 virus with an ESEV motif and a mutant virus with an NS1 protein containing a C-terminal RSKV motif by reverse genetics. We compared the phenotypes of these viruses in vitro in human, mouse, and duck cells as well as in vivo in mice and ducks. In human cells, the human C-terminal RSKV domain increased virus replication. In contrast, the avian Cterminal ESEV motif of NS1 increased virulence in mice. We linked this increase in pathogenicity in mice to an increase in virus replication and to a more severe lung inflammation associated with a higher level of production of type I interferons. Interestingly, the human C-terminal RSKV motif of NS1 increased viral replication in ducks. H7N1 virus with a C-terminal RSKV motif replicated to higher levels in ducks and induced higher levels of Mx, a type I interferon-stimulated gene. Thus, we identify the C-terminal domain of NS1 as a species-specific virulence domain.

Item Type:Article
Additional Information:Thanks to American Society for Microbiology editor. The original PDF of the article can be found at : http://jvi.asm.org/cgi/content/abstract/84/13/6733
Audience (journal):International peer-reviewed journal
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Institution: Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT
French research institutions > Institut National de la Recherche Agronomique - INRA
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Deposited By: SYLVIE OUDDANE

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