Species-specific Contribution of the Four C-terminal Amino Acids of Influenza A NS1 Protein to Virulence

[tetano]

J Virol. 2010 Apr 21. [Epub ahead of print]
Species-specific Contribution of the Four C-terminal Amino Acids of Influenza A NS1 Protein to Virulence.

Soubies SM, Volmer C, Croville G, Loupias J, Peralta B, Costes P, Lacroux C, Gu?rin JL, Volmer R.

INRA, UMR 1225, Ecole nationale v?t?rinaire de Toulouse, F-31076 Toulouse, France; Universit? de Toulouse; ENVT; UMR 1225; F-31076 Toulouse, France.
Abstract

Large-scale sequence analyses of influenza viruses revealed that non-structural 1 (NS1) proteins from avian influenza viruses have a conserved C-terminal ESEV amino acid motif, while NS1 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 by reverse genetics a wild-type H7N1 virus with a ESEV motif and a mutant virus with a NS1 containing a C-terminal RSKV motif. We compared the phenotype of these viruses in vitro in human, mice and duck cells, as well as in vivo in mice and ducks. In human cells, the human C-terminal RSKV domain increased virus replication. By contrast, the avian C-terminal ESEV motif of NS1 increased virulence in mice. We could link this increase in pathogenicity in mice to an increase in virus replication and to a more severe lung inflammation associated with a higher 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 interferons stimulated gene. Thus, we identify the C-terminal domain of NS1 as a species-specific virulence domain.

PMID: 20410267 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/pubmed/20410267?dopt=Abstract

 

[Giuseppe]

Re: Species-specific Contribution of the Four C-terminal Amino Acids of Influenza A NS1 Protein to Virulence

[Source: US National Library of Medicine, (LINK). Edited.]

J Virol. 2010 Apr 21. [Epub ahead of print]

Species-specific Contribution of the Four C-terminal Amino Acids of Influenza A NS1 Protein to Virulence.

Soubies SM, Volmer C, Croville G, Loupias J, Peralta B, Costes P, Lacroux C, Gu?rin JL, Volmer R. - INRA, UMR 1225, Ecole nationale v?t?rinaire de Toulouse, F-31076 Toulouse, France; Universit? de Toulouse; ENVT; UMR 1225; F-31076 Toulouse, France.

Large-scale sequence analyses of influenza viruses revealed that non-structural 1 (NS1) proteins from avian influenza viruses have a conserved C-terminal ESEV amino acid motif, while NS1 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 by reverse genetics a wild-type H7N1 virus with a ESEV motif and a mutant virus with a NS1 containing a C-terminal RSKV motif. We compared the phenotype of these viruses in vitro in human, mice and duck cells, as well as in vivo in mice and ducks. In human cells, the human C-terminal RSKV domain increased virus replication. By contrast, the avian C-terminal ESEV motif of NS1 increased virulence in mice. We could link this increase in pathogenicity in mice to an increase in virus replication and to a more severe lung inflammation associated with a higher 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 interferons stimulated gene. Thus, we identify the C-terminal domain of NS1 as a species-specific virulence domain.

PMID: 20410267 [PubMed - as supplied by publisher]
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