|Solorzano, Alicia - MOUNT SINAI SCHOOL OF MED|
|Webby, Richard - ST. JUDE CHILDRENS RESEAR|
|Garcia-Sastre, Adolfo - MOUNT SINAI SCHOOL OF MED|
Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2004
Publication Date: July 10, 2004
Citation: Solorzano, A., Webby, R.J., Lager, K.M., Richt, J.A., Garcia-Sastre, A. 2004. The NS1 protein of influenza a virus is a determinant of virulence in vivo. 23rd Annual Meeting of the American Society for Virology. Paper No. W34-3. 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.