Swine influenza A virus isolates containing the pandemic H1N1 origin matrix gene elicit greater disease in the murine model

ABSTRACT Since the 1990’s, endemic North American swine influenza A viruses (swFLUAV) contained an internal gene segment constellation referred to as the triple reassortment internal gene (TRIG) cassette. In 2009, the H1N1 pandemic (pdmH1N1) virus spilled back into swine, but did not become endemic. However, the pdmH1N1 did contribute the matrix gene segment (pdmM) to the swFLUAVs circulating in the pig population; which replaced the classical swine matrix gene (swM) found in the TRIG cassette, suggesting that the pdmM has a fitness benefit. Others have shown that swFLUAV containing the pdmM have greater neuraminidase activity and transmission efficiency compared to viruses containing the swM gene segment. We hypothesized that the matrix gene could also affect disease and utilized two infection models, resistant BALB/c and susceptible DBA/2 mice, to assess swFLUAV pathogenicity. We infected BALB/c and DBA/2 mice with a panel of H1 and H3 swFLUAVs containing the swM or pdmM gene and measured lung virus titers, morbidity, mortality, and lung histopathology. H1 influenza strains containing the pdmM gene caused greater morbidity and mortality in both resistant and susceptible murine strains, while H3 swFLUAVs caused no clinical disease. However, both H1 and H3 swFLUAVs containing the pdmM replicated to higher viral titers in the lungs and pdmM containing H1 viruses induced greater histological changes compared to swM H1 viruses. While the surface glycoproteins contribute to swFLUAV pathogenicity, and other genes also influence disease, these data suggest that the origin of the matrix gene also contributes to pathogenicity of swFLUAV viruses in mice.