Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs

Alicia Solórzano, Richard J. Webby, Kelly M. Lager, Bruce H. Janke, Adolfo García-Sastre, Jürgen A. Richt

Research output: Contribution to journalArticlepeer-review

212 Scopus citations

Abstract

It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-α/β) antagonist, both in vitro and in experimental animal model systems. However, evidence of this function in a natural host has not yet been obtained. Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by using reverse genetics. The virulent wild-type A/Swine/Texas/4199-2/98 (TX/98) virus and various mutants encoding carboxy-truncated NS1 proteins were rescued. Growth properties of TX/98 viruses with mutated NS1, induction of IFN in tissue culture, and virulence-attenuation in pigs were analyzed and compared to those of the recombinant wild-type TX/98 virus. Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent IFN-α/α synthesis in pig cells. Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-α/β induced in vitro. These data suggest that the NS1 protein of SIV is a virulence factor. Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SFV infections of pigs.

Original languageEnglish
Pages (from-to)7535-7543
Number of pages9
JournalJournal of Virology
Volume79
Issue number12
DOIs
StatePublished - Jun 2005

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