Swine Acute Diarrhea Syndrome Coronavirus Induces Autophagy to Promote Its Replication via the Akt/mTOR Pathway

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an enveloped, single‐stranded, positive‐sense RNA viruse belonging to Coronaviridae family. An increasing number of studies have demonstrated that viruses could utilize autophagy to promote their own replication. However, the relationship between SADS-CoV and autophagy machinery remained unknown. Here, we reported that SADS-CoV infection induced autophagy in cultured cells and pharmacologically increased autophagy was conducive to viral proliferation. Conversely, suppression of autophagy by pharmacological inhibitor or knockdown of autophagy-related protein impeded viral replication. Furthermore, we demonstrated the underlying mechanisms by which SADS-CoV triggered autophagy through inactivation of the Akt/mTOR pathway. Importantly, we identified integrin α3 (ITGA3) as a potential antiviral target upstream of Akt/mTOR and autophagy pathways by analyzing the proteomic profiles. Knockdown of ITGA3 using RNA inference activated autophagy and as a consequence, increased the replication of SADS-CoV. Collectively, our studies revealed a novel mechanism that SADS-CoV induced autophagy to facilitate its proliferation via Akt/mTOR pathway and found that ITGA3 is an effective antiviral factor for suppressing viral infection.