ArticlemBio2024
The E3 ligase TRIM22 restricts SARS-CoV-2 replication by promoting proteasomal degradation of NSP8.
Article in mBio, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.Microbiology spectrum · 2026Trial
- Article
- Host OTUB2 and viral PLpro stabilize NSP8 to promote SARS-CoV-2 replication.Virologica Sinica · 2026Article
- Insights into SARS-CoV-2 replication controlActa pharmaceutica Sinica. B · 2026Article
- SARS-CoV-2 ORF3a suppresses host antiviral interferon responses by promoting STUB1-mediated PTEN proteasomal degradation.Journal of virology · 2026Article
- ZFP91 restricts RSV replication by driving K48-linked ubiquitination and proteasomal degradation of M2-1.Cellular and molecular life sciences : CMLS · 2026Article
- E3 ubiquitin ligase NEDD4 inhibits PEDV infection through ubiquitination and degradation of the viral primase NSP8.Journal of virology · 2026Article
- Shift work disrupts Immune regulation of the transcriptome in hospital nurses.Frontiers in public health · 2026Article
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- SARS-CoV-2-host and interactions: the dual roles of E3 ubiquitin ligases and ubiquitin-like modification mechanisms in viral infection.Frontiers in immunology · 2026Review
- The role of TRIM proteins in the pathogenesis of mycobacterium tuberculosis.Biology direct · 2025Review
- The C-terminal Domain of SARS-CoV-2 nsp8 is a Molten Globule in the Absence of Binding Partners.Journal of molecular biology · 2025Article
- NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The ELF3-TRIM22-MAVS signaling axis regulates type I interferon and antiviral responses.Journal of virology · 2025Article
- Article
- TRIM22 governs tumorigenesis and protects against endometrial cancer-associated cachexia by inhibiting inflammatory response and adipose thermogenic activity.Cancer & metabolism · 2025Article
- TRIM22 promotes glioblastoma development by ubiquitinating Bcl-2.Molecular & cellular oncology · 2025Article
- Lung-Targeted Lipid Nanoparticle-Delivered siUSP33 Attenuates SARS-CoV-2 Replication and Virulence by Promoting Envelope Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Human E3 ubiquitin ligases: accelerators and brakes for SARS-CoV-2 infection.Biochemical Society transactions · 2024Review
- TRIMming down Flavivirus Infections.Viruses · 2024Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is mediated by a complex of non-structural proteins (NSPs), of which NSP7 and NSP8 serve as subunits and play a key role in promoting the activity of RNA-dependent RNA polymerase (RdRp) of NSP12. However, the stability of subunits of the RdRp complex has rarely been reported. Here, we found that NSP8 was degraded by the proteasome in host cells, and identified tripartite motif containing 22 (TRIM22) as its E3 ligase. The interferon (IFN) signaling pathway was activated upon viral invasion into host cells, and TRIM22 expression increased. TRIM22 interacted with NSP8 and ubiquitinated it at Lys97 via K48-type ubiquitination. TRIM22 overexpression significantly reduced viral RNA and protein levels. Knockdown of TRIM22 enhanced viral replication. This study provides a new explanation for treating patients suffering from SARS-CoV-2 with IFNs and new possibilities for drug development targeting the interaction between NSP8 and TRIM22.IMPORTANCENon-structural proteins (NSPs) play a crucial role in the replication of severe acute respiratory syndrome coronavirus 2, facilitating virus amplification and propagation. In this study, we conducted a comprehensive investigation into the stability of all subunits comprising the RNA-dependent RNA polymerase complex. Notably, our results reveal for the first time that NSP8 is a relatively unstable protein, which is found to be readily recognized and degraded by the proteasome. This degradation process is mediated by the host E3 ligase tripartite motif containing 22 (TRIM22), which is also a member of the interferon stimulated gene (ISG) family. Our study elucidates a novel mechanism of antiviral effect of TRIM22, which utilizes its own E3 ubiquitin ligase activity to hinder viral replication by inducing ubiquitination and subsequent degradation of NSP8. These findings provide new ideas for the development of novel therapeutic strategies. In addition, the conserved property of NSP8 raises the possibility of developing broad antiviral drugs targeting the TRIM22-NSP8 interaction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.