Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication.
J Cell Biol
; 222(7)2023 07 03.
Article
in English
| MEDLINE | ID: covidwho-2305708
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Organelles
/
Endoplasmic Reticulum
/
SARS-CoV-2
/
Membrane Proteins
Type of study:
Etiology study
Topics:
Variants
Limits:
Humans
Language:
English
Year:
2023
Document Type:
Article
Affiliation country:
Jcb.202203060
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