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Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication.
Williams, Jeffrey M; Chen, Yu-Jie; Cho, Woo Jung; Tai, Andrew W; Tsai, Billy.
  • Williams JM; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Chen YJ; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Cho WJ; Biomedical Research Core Facilities, University of Michigan Medical School , Ann Arbor, MI, USA.
  • Tai AW; Department of Internal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Tsai B; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
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.
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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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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