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

GSE268640 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/07/31 Platform GPL18480
Summary
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 mouse model. A recombinant M-K14/K15R virus showed reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.
Published in
TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication
Gonzalez-Orozco M, Tseng HC, Hage A et al. · bioRxiv : the preprint server for biology 2024 · PMID 38948778 · doi:10.1101/2024.06.17.599107
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Also filed as BioProject PRJNA1117951 and SRA study SRP510690. Searching any of these in the dataset finder brings you back here.

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