Sorting Nexin 10 Mediates Endosomal Acidification and Autophagy to Promote Influenza A Virus Infection

The infection cycle of the Influenza A Virus (IAV) typically requires host factors to regulate replication and proliferation. However, the roles of these factors remain undiscovered. This study focuses on Sorting Nexin 10 (SNX10), which is involved in regulating membrane trafficking and endosomal stabilization. Our previous study identified that SNX10 facilitates the replication of human coronavirus OC43 through enhancing clathrin-mediated endocytosis. In our present study, we found that SNX10 significantly promoted IAV infection in host cells. The conditional knockout of Snx10 in mice lungs prolonged survival following IAV challenge. Mechanistically, SNX10 facilitated the production of acidic endosomal vesicles and promoted the accumulation of pro-viral autophagic structures, a process supported by the specific interaction between SNX10 and the viral NP and M2 protein of IAV. Blocking SNX10-mediated acidic endosomal vesicles and autophagosome formation demonstrated antiviral effects. Moreover, IAV infection increased SNX10 protein levels by suppressing its ubiquitination, suggesting that SNX10 could serve as a potential host-derived antiviral drug target.