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. Here we show that the host E3-ubiquitin ligase TRIM7 acts as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7^-/- mice exhibit 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 reveal that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model

SUBMITTER: Gonzalez-Orozco M 

PROVIDER: S-EPMC11608229 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature