title: Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs.
abstract: It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-alpha/beta) 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-alpha/beta synthesis in pig cells. Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-alpha/beta 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 SIV infections of pigs.
authors.affiliation: National Animal Disease Center, Ames, IA 50010, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Solórzano
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Lager
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Janke
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Richt
mesh_terms: D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D007251:Influenza, Human / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009154:Mutation; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014774:Virulence; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; D016898:Interferon-alpha; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta