Professor Ricardo Rajsbaum moved his lab from the University of Texas Medical Branch to Rutgers Health Institute for Infectious & Inflammatory Diseases (i3D) in 2022. He is now the Director of the Center for Virus-Host-Innate Immunity. His group at Rutgers and UTMB studied the pathogenesis of SARS-CoV-2, which involves excessive inflammation and viral-induced cell death. The work investigates the potential antiviral and immune regulatory functions of host E3 ubiquitin ligase TRIM& and its effects on the viral membrane (M) protein in inhibiting apoptosis.
- TRIM7 ubiquitinates the SARS-CoV-2 M protein on the K14 residue, which protects cells from apoptosis and limits viral replication.
- Trim7 knockout mice exhibit increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses.
- Mutations on the M-K14 residue, which prevent TRIM7-mediated ubiquitination, were identified in circulating SARS-CoV-2 variants during the pandemic, suggesting a potential role in viral pathogenesis.
The paper points out that TRIM7 has antiviral effects against SARS-CoV-2 through multiple mechanisms, including ubiquitination of the M protein, immune response regulation, and IFN signaling modulation. They also identified naturally occurring mutations in circulating strains in the viral M protein that could impact pathogenicity (K14, K15). While they say these mutations are relatively low and do not correlate with a specific variant of concern, these mutations could indicate that these strains are potentially more pathogenic. Therefore, they propose monitoring mutations on the M protein in infected individuals might predict disease severity if the effects can be correlated with clinical profiles in infected patients.
The multiple functions of TRIM7 during SARS-CoV-2 infection
Gonzalez-Orozco M, Tseng HC, Hage A, Xia H, Behera P, Afreen K, Peñaflor-Tellez Y, Giraldo MI, Huante M, Puebla-Clark L, van Tol S, Odle A, Crown M, Teruel N, Shelite TR, Moreno-Contreras J, Terasaki K, Makino S, Menachery V, Endsley M, Endsley JJ, Najmanovich RJ, Bashton M, Stephens R, Shi PY, Xie X, Freiberg AN, Rajsbaum R. TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication. Nat Commun. 2024 Nov 30;15(1):10438. doi: 10.1038/s41467-024-54762-5. PMID: 39616206; PMCID: PMC11608229. https://www.nature.com/articles/s41467-024-54762-5
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