tetano
Editor, Senior Moderator
Cell Rep
. 2023 Mar 10;42(4):112286.
doi: 10.1016/j.celrep.2023.112286. Online ahead of print.
Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication
Xuan Tan[SUP] 1 [/SUP], Kun Cai[SUP] 2 [/SUP], Jiajia Li[SUP] 3 [/SUP], Zhen Yuan[SUP] 1 [/SUP], Ruifeng Chen[SUP] 1 [/SUP], Hurong Xiao[SUP] 1 [/SUP], Chuanrui Xu[SUP] 3 [/SUP], Bing Hu[SUP] 2 [/SUP], Yali Qin[SUP] 4 [/SUP], Binbin Ding[SUP] 5 [/SUP]
Affiliations
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.
. 2023 Mar 10;42(4):112286.
doi: 10.1016/j.celrep.2023.112286. Online ahead of print.
Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication
Xuan Tan[SUP] 1 [/SUP], Kun Cai[SUP] 2 [/SUP], Jiajia Li[SUP] 3 [/SUP], Zhen Yuan[SUP] 1 [/SUP], Ruifeng Chen[SUP] 1 [/SUP], Hurong Xiao[SUP] 1 [/SUP], Chuanrui Xu[SUP] 3 [/SUP], Bing Hu[SUP] 2 [/SUP], Yali Qin[SUP] 4 [/SUP], Binbin Ding[SUP] 5 [/SUP]
Affiliations
- 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.