Swine ANP32A supports avian influenza virus polymerase

Abstract

Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as mixing vessels, being susceptible to both avian and human origin viruses, which allows the emergence of novel reassortants, such as the precursor to the 2009 H1N1 pandemic. ANP32 proteins are host factors that act as influenza virus polymerase cofactors. In this study we describe how swine ANP32A, uniquely among the mammalian ANP32 proteins tested, supports some, albeit limited, activity of avian origin influenza virus polymerases. We further show that after the swine-origin influenza virus emerged in humans and caused the 2009 pandemic it evolved polymerase gene mutations that enabled it to more efficiently use human ANP32 proteins. We map the super pro-viral activity of swine ANP32A to a pair of amino acids, 106 and 156, in the LRR and central domains and show these mutations enhance binding to influenza virus trimeric polymerase. These findings help elucidate the molecular basis for the mixing vessel trait of swine and further our understanding of the evolution and ecology of viruses in this host.