SURVEY OF INTRASPECIFIC VARIATION WITHIN SWINE ANP32A/B AND EFFECTS ON HOST PERMISSIVENESS TO AVIAN INFLUENZA VIRUS

The overall goal of this proposal is to provide feasible means of limiting the emergence of mammalian adapted avian influenza virus (AIV) strains by decreasing the suitability of domestic swine populations to serve as endemic AIV and reassortant reservoirs.Specifically, this proposal aims to identify acidic leucine-rich nuclear phosphoprotein 32 (ANP32) variants and isoforms present in domestic swine that modulate AIV polymerase activity through the following objectives: 1) Discovery of ANP32A/B polymorphisms and isoforms across domestic swine using large-scale comparative genomics, and 2) Assess the effect of selected ANP32A/B variants and isoforms on influenza A polymerase binding and activity through in vitro CRISPR-cas9 gene editing and functional assays.