tetano
Editor, Senior Moderator
J Cell Biol
. 2023 Jul 3;222(7):e202203060.
doi: 10.1083/jcb.202203060. Epub 2023 Apr 24.
Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication
Jeffrey M Williams[SUP] #[/SUP][SUP] 1 [/SUP], Yu-Jie Chen[SUP] #[/SUP][SUP] 1 [/SUP], Woo Jung Cho[SUP] 2 [/SUP], Andrew W Tai[SUP] 3 [/SUP], Billy Tsai[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.
. 2023 Jul 3;222(7):e202203060.
doi: 10.1083/jcb.202203060. Epub 2023 Apr 24.
Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication
Jeffrey M Williams[SUP] #[/SUP][SUP] 1 [/SUP], Yu-Jie Chen[SUP] #[/SUP][SUP] 1 [/SUP], Woo Jung Cho[SUP] 2 [/SUP], Andrew W Tai[SUP] 3 [/SUP], Billy Tsai[SUP] 1 [/SUP]
Affiliations
- PMID: 37093123
- DOI: 10.1083/jcb.202203060
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.