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United States Department of Agriculture

Agricultural Research Service

Title: Mutations in the Ns1 Protein of Swine Influenza Virus Impairs Anti-Interferon Activity and Confers Attenuation in Pigs

Authors
item Solorzano, Alicia - MOUNT SINAI SCHOOL OF MED
item Webby, Richard - ST JUDE CHILDREN'S RESEAR
item Lager, Kelly
item Janke, Bruce - IOWA STATE UNIVERSITY
item Garcia-Sastre, Adolfo - MOUNT SINAI SCHOOL OF MED
item Richt, Juergen

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 7, 2005
Publication Date: June 1, 2005
Citation: Solorzano, A., Webby, R.J., Lager, K.M., Janke, B.H., Garcia-Sastre, A., Richt, J.A. 2005. Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. Journal of Virology. 79(12):7535-7543.

Interpretive Summary: Swine influenza (SI) is an acute respiratory disease of swine that is caused by swine influenza virus (SIV), a type A influenza virus. The non structural protein 1 of influenza A viruses have been shown to inhibit the induction of the anti-viral action of the type I interferon (IFN) system as shown in cell culture and experimental animal model systems. This ability confers to the virus the capacity to evade the host innate anti-viral immune response. However, evidence of this function in a natural host of influenza A, like the pig, has not yet been obtained. In the present study, the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs was investigated using a newly developed reverse genetics system. The virulent wild-type TX/98 virus (an H3N2 SIV) and various recombinant TX/98 SIVs encoding partially truncated NS1 proteins were generated in vitro. Growth properties and capability to induce type I IFN in tissue culture as well as virulence/attenuation in pigs of NS1-mutated TX/98 viruses were analyzed and compared to the wild-type TX/98 virus. Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent type I IFN synthesis in pig cells. Moreover, all NS1 mutant viruses were attenuated in pigs and their levels of attenuation correlated with the amounts of type I IFN induced in vitro. These data indicate that the NS1 protein of TX/98 swine influenza virus is a virulence factor and that its mode of action is most likely via the modulation of the pig type I IFN response. Due to their attenuation in pigs, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections.

Technical Abstract: Swine influenza (SI) is an acute respiratory disease of swine that is caused by swine influenza virus (SIV), a type A influenza virus. It is known that the NS1 protein of influenza virus attenuates the induction of type I interferon (IFN) and confers to the virus the capacity to evade the host IFN innate immune system in experimental animal model systems. However, evidence of this function in a natural host has not yet been obtained. In the present study, the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs was investigated using a newly developed reverse genetics system. The virulent wild-type TX/98 virus (an H3N2 SIV) and various recombinant TX/98 SIVs encoding partially carboxy-terminally truncated NS1 proteins were generated. Growth properties and capability to induce type I IFN in tissue culture as well as virulence/attenuation in pigs of NS1-mutated TX/98 viruses were analyzed and compared to the plasmid-derived wild-type TX/98 virus. Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent type I IFN synthesis in pig cells. Moreover, all NS1 mutant viruses were attenuated in pigs and their levels of attenuation correlated with the amounts of type I IFN induced in vitro. These data indicate that the NS1 protein of TX/98 swine influenza virus is a virulence factor and that its mode of action is most likely via the modulation of the pig type I IFN response. Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections of pigs.

Last Modified: 12/20/2014
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