Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/7/2010
Publication Date: 7/17/2010
Citation: Buehler, J., Mccullough, D., Loving, C.L., Vincent, A.L., Lager, K.M., Miller, C. 2010. Investigation of the Function of the Influenza A Virus PB1-F2 Protein During Infection of Swine and Human Cells with a Predominant Circulating Swine Virus Isolate [abstract]. American Society for Virology Meeting. p. 279. Interpretive Summary:
Technical Abstract: In recent years a protein referred to as PB1-F2 was discovered in a second open reading frame of the PB1 gene of many influenza A viruses. Studies have indicated that PB1-F2 may induce apoptosis of infected cells, increase susceptibility to secondary bacterial infection in mice, increase macrophage and neutrophil infiltration in the lungs, and have beta-defensin activity. However, the majority of previous studies were done in either human cell lines, or in mice, using influenza strains that are either mouse adapted or human, leaving a gap in understanding the role of PB1-F2 in a natural animal host, the pig. As reinforced by the emergence of a swine-origin pandemic influenza virus in 2009, research aimed at identifying pathogenic mechanisms of circulating swine influenza viruses in pigs and people is important for animal health and for assessing potential human health risks of swine-origin influenza. In this study, we have utilized an isolate of influenza virus from North American swine that is representative of predominant circulating strains to examine the role of PB1-F2 in swine influenza virus pathogenicity. Interestingly, this isolate shows substantial divergence in the sequence of the PB1-F2 protein when compared with other commonly studied human or mouse-adapted strains. Reverse genetics was employed to create a recombinant virus from this isolate, and mutations were introduced into the recombinant virus such that PB1-F2 expression was knocked-out. Recombinant viruses with and without PB1-F2 expression are being used to examine the role of PB1-F2 in influenza infection of both porcine and human cell lines with regard to the rate of replication, mitochondrial association, and capacity to induce apoptosis. This work should elucidate the impact of swine PB1-F2 expression on swine and human cells and begin to identify strain-specific or host-specific functions of PB1-F2 in influenza A virus pathogenicity.