TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication.

ABSTRACT: SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7 ^-/- mice exhibited increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients revealed that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a m

SUBMITTER: Gonzalez-Orozco M 

PROVIDER: S-EPMC11212893 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature