Skip to main content
ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #279095

Title: Pathogenicity of swine influenza viruses possessing an avian or swine-origin PB2 polymerase gene evaluated in mouse and pig models

item MA, WENJUN - Iowa State University
item Lager, Kelly
item LI, XI - Harbin Veterinary Research Institute
item JANKE, BRUCE - Iowa State University
item MOSIER, DEREK - Kansas State University
item PAINTER, LAURA - Iowa State University
item Ulery, Eva
item MA, JINGQUN - Kansas State University
item LEKCHAROENSUK, PORNTIPPA - Kasetsart University
item WEBBY, RICHARD - St Jude Children’s Research Hospital
item Richt, Juergen

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/2010
Publication Date: 2/5/2011
Citation: Ma, W., Lager, K.M., Li, X., Janke, B.H., Mosier, D.A., Painter, L.E., Ulery, E.S., Ma, J., Lekcharoensuk, P., Webby, R.J., Richt, J.A. 2011. Pathogenicity of swine influenza viruses possessing an avian or swine-origin PB2 polymerase gene evaluated in mouse and pig models. Virology. 410(1):1-6.

Interpretive Summary: Although influenza type A viruses are capable of infecting many different avian and mammalian species, not all influenza A viruses can infect all susceptible species. The factors that regulate which virus might infect which species are not completely understood. One limiting factor is the genetics of the virus can regulate how efficiently an influenza virus might replicate in a host. Influenza A viruses isolated from birds have a genetic sequence in one gene that is considered to be an "avian signature." It is slightly different from the influenza A viruses isolated from humans that have a "mammalian signature" at the same location in the same viral gene. These respective differences can contribute to how influenza A virus replicates in birds and humans. Much of this understanding has been derived from mouse models studying how influenza A viruses interact with a host. Swine can be infected with both avian and human influenza A viruses. We examined how a mammalian-like virus with the avian signature, and an avian-like virus with the mammalian signature replicated in pigs and in a mouse model. As would be predicted, mutating the mammalian virus reduced replication in the mouse, and adding the mammalian signature to the avian virus increased the ability of the virus to replicate in mice. Interestingly, this was not the case when the viruses were given to pigs demonstrating that the virus-host interactions are very complicated and there may be many unique interactions that are dependent on multiple host and viral factors.

Technical Abstract: Influenza A viruses isolated from birds normally contain a PB2 polymerase gene with the avian-signature glutamic acid (E) at position 627, while those isolated from humans contain the mammalian-signature lysine (K) at this position. This residue has been shown to be a determinant of host range and contributes to the pathogenesis of human, avian and mouse-adapted influenza viruses in the mouse model. In this study, we tried to analyze the contribution of a swine and avian origin PB2 carrying either 627K or 627E in mouse and pig models. For this purpose, four recombinant viruses were generated by reverse genetics: the original wild-type 1930 virus with swine PB2 627K (1930-PB2-627K), a mutated 1930 virus with swine PB2 627E (1930-PB2-627E), 1930 virus with an avian PB2 627E (1930-Tx/98PB2-627E) and a mutated 1930-Tx/PB2 with 627K (1930-Tx/98PB2-627K). The avian PB2 polymerase gene was derived from an H3N2 swine virus [A/Swine/Texas/4199-2/98 (Tx/98)]. In the mouse model, the virulence of the 1930-Tx/98PB2-627E was significantly increased when E at position 627 of PB2 was changed to K while the virulence of wild-type 1930-PB2-627K was significantly decreased when the K at position 627 of PB2 was mutated to an E. In the pig model, the wild-type 1930-PB2-627K caused more macroscopic and histopathologic lung lesions in pigs when compared to the mutated 1930-PB2-627E virus. This effect was not seen when the Tx/98 PB2 with 627K was used. In conclusion, within the background of the classical swine H1N1 virus, 627K of PB2 is critical for virulence in the mouse model, independent of whether PB2 is derived from swine or avian influenza viruses. In contrast, the origin (avian vs. mammalian) of the PB2 gene determines importance of position 627 for pathogenicity in pigs.