SARS-CoV-2 Nsp2 recruits GIGYF2 near viral replication sites and supports viral protein production.

ABSTRACT: The SARS-CoV-2 genome encodes 16 nonstructural proteins (Nsps), with Nsp2 being the least conserved and understood. This study highlights a crucial role for Nsp2 in the early phase of the viral life cycle, particularly its interaction with GIGYF2, which relocates near double-membrane vesicles (DMVs) and enhances viral protein production. Deletion of the Nsp2-coding region from the viral genome led to a drastic reduction in viral RNA synthesis early in infection (3-4 h after infection). Interactome analysis in virus-infected cells identified GIGYF2, a host-encoded translational regulation protein, as a key Nsp2 partner. This interaction was confirmed for both SARS-CoV-1 and SARS-CoV-2. Depletion of GIGYF2 or its cofactor ZNF598 phenocopied the replication defects observed with Nsp2 deletion

SUBMITTER: Kim J 

PROVIDER: S-EPMC12288870 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature