PA-X 122V broadly determines the host shutoff activity of influenza A viruses

PA gene, encoding PA protein and several accessory proteins including PA-X, PA-N155, and PA-N182, is a key factor determining the pathogenicity of influenza A virus. In this study, we found that PA-X is crucial for suppression of host protein synthesis during viral infection. Loss of PA-X expression significantly reduced its host shutoff activity, thereby enhancing host antiviral immune responses. Furthermore, we pinpointed a crucial amino acid, 122V, involved in the host shutoff activity of PA-X and found that 122V is highly conserved among multiple subtypes of influenza A viruses. These findings deepen our understanding of the mechanisms by which PA-X modulates viral pathogenesis and the host immune response.