The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle.

ABSTRACT: SARS-CoV-2, like other coronaviruses, builds a membrane-bound replication organelle to enable RNA replication¹. The SARS-CoV-2 replication organelle is composed of double-membrane vesicles (DMVs) that are tethered to the endoplasmic reticulum (ER) by thin membrane connectors², but the viral proteins and the host factors involved remain unknown. Here we identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 replication organelle. NSP3 and NSP4 generate the DMVs, whereas NSP6, through oligomerization and an amphipathic helix, zippers ER membranes and establishes the connectors. The NSP6(ΔSGF) mutant, which arose independently in the Alpha, Beta, Gamma, Eta, Iota and Lambda variants of SARS-CoV-2, behaves as a gain-of-function mutant with a higher

SUBMITTER: Ricciardi S 

PROVIDER: S-EPMC7612910 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature