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NS1-Mediated Delay of Type I Interferon Induction Contributes to Influenza A Virulence in Ferrets

tetano

Editor, Senior Moderator
J Gen Virol. 2011 Mar 16. [Epub ahead of print]
NS1-Mediated Delay of Type I Interferon Induction Contributes to Influenza A Virulence in Ferrets.

Meunier I, von Messling V.

INRS-Institut Armand-Frappier.
Abstract

The interference of the influenza A non-structural protein NS1 with type I interferon (IFN) signaling has been extensively characterized in vitro. To assess the contribution of NS1 to the virulence of a specific strain, we generated recombinant USSR/90/77 viruses bearing the NS1 proteins of the attenuated strain PR/8/34 or the highly pathogenic 1918 "Spanish flu", all belonging to the H1N1 subtype. In vitro, the extent of interference with type I IFN production exerted by the different NS1 proteins correlated with the reported virulence of the respective strain. Infection of ferrets with the recombinant viruses revealed that the presence of the 1918 NS1 resulted in a slightly more severe disease with overall higher clinical scores and increased lung pathology. Analysis of mRNA from nasal wash cells revealed that the viruses carrying the 1918 and, to a lesser extent, USSR/90/77 NS1 proteins resulted in a delay in upregulation of type I IFNs compared to the NS1 PR/8/34-expressing virus, demonstrating the importance of NS1 for early host response control and virulence.

PMID: 21411677 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21411677
 
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