Swine acute diarrhea syndrome coronavirus induces autophagy to promote its replication via the Akt/mTOR pathway

  • iScience. 2022 Nov 18;25(11):105394. doi: 10.1016/j.isci.2022.105394.
Siying Zeng  1 Yan Zhao  1 Ouyang Peng  1 Yu Xia  1 Qiuping Xu  2  3 Hongmei Li  4 Chunyi Xue  1 Yongchang Cao  1 Hao Zhang  1
Affiliations
  • 1. State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 3. Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 4. School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Abstract

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an enveloped, single-stranded, positive-sense RNA virus belonging to the Coronaviridae family. Increasingly studies have demonstrated that viruses could utilize Autophagy to promote their own replication. However, the relationship between SADS-CoV and Autophagy remains unknown. Here, we reported that SADS-CoV infection-induced Autophagy and pharmacologically increased Autophagy were conducive to viral proliferation. Conversely, suppression of Autophagy by pharmacological inhibitors or knockdown of autophagy-related protein impeded viral replication. Furthermore, we demonstrated the underlying mechanism by which SADS-CoV triggered Autophagy through the inactivation of the Akt/mTOR pathway. Importantly, we identified Integrin α3 (ITGA3) as a potential Antiviral target upstream of Akt/mTOR and Autophagy pathways. Knockdown of ITGA3 enhanced Autophagy and consequently 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 was an effective Antiviral factor for suppressing viral Infection.

Keywords
Biological sciences; cell biology; virology.