2. Academic Validation
  3. Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication

Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication

  • Cell Rep. 2023 Apr 25;42(4):112286. doi: 10.1016/j.celrep.2023.112286.
Xuan Tan 1,  Kun Cai 2,  Jiajia Li 3,  Zhen Yuan 1,  Ruifeng Chen 1,  Hurong Xiao 1,  Chuanrui Xu 3,  Bing Hu 2,  Yali Qin 4,  Binbin Ding 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • 2 Institute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei 430079, China.
  • 3 School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • 4 State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: [email protected].
  • 5 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Cell Architecture Research Institute, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: [email protected].
PMID: 36952345 DOI: 10.1016/j.celrep.2023.112286
Abstract

ER-phagy is a form of Autophagy that is mediated by ER-phagy receptors and selectively degrades endoplasmic reticulum (ER). Coronaviruses have been shown to use the ER as a membrane source to establish their double-membrane vesicles (DMVs). However, whether viruses modulate ER-phagy to drive viral DMV formation and its underlying molecular mechanisms remains largely unknown. Here, we demonstrate that coronavirus subverts ER-phagy by hijacking the ER-phagy receptors FAM134B and ATL3 into p62 condensates, resulting in increased viral replication. Mechanistically, we show that viral protein ORF8 binds to and undergoes condensation with p62. FAM134B and ATL3 interact with homodimer of ORF8 and are aggregated into ORF8/p62 liquid droplets, leading to ER-phagy inhibition. ORF8/p62 condensates disrupt ER-phagy to facilitate viral DMV formation and activate ER stress. Together, our data highlight how coronavirus modulates ER-phagy to drive viral replication by hijacking ER-phagy receptors.

Keywords

CP: Microbiology; ER stress; ER-phagy; ORF8; SARS-CoV-2; double membrane vesicles; p62 condendation.

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