冠状病毒通过劫持 FAM134B 和 ATL3 进入 p62 凝聚物来颠覆内质网自噬，从而促进病毒复制。
Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication.
机构信息
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Institute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei 430079, China.
出版信息
Cell Rep. 2023 Apr 25;42(4):112286. doi: 10.1016/j.celrep.2023.112286. Epub 2023 Mar 10.
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.
ER 自噬是一种由 ER 自噬受体介导的自噬形式，选择性降解内质网 (ER)。已经表明冠状病毒利用 ER 作为膜源来建立它们的双膜囊泡 (DMVs)。然而，病毒是否调节 ER 自噬来驱动病毒 DMV 的形成及其潜在的分子机制在很大程度上仍然未知。在这里，我们证明冠状病毒通过劫持 ER 自噬受体 FAM134B 和 ATL3 进入 p62 凝聚物来颠覆 ER 自噬，导致病毒复制增加。在机制上，我们表明病毒蛋白 ORF8 与 p62 结合并发生凝聚。FAM134B 和 ATL3 与 ORF8 的同源二聚体相互作用并聚集到 ORF8/p62 液滴中，导致 ER 自噬抑制。ORF8/p62 凝聚物破坏 ER 自噬，促进病毒 DMV 的形成并激活 ER 应激。总之，我们的数据强调了冠状病毒如何通过劫持 ER 自噬受体来调节 ER 自噬以驱动病毒复制。
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