ArticleJournal of virology2019
Hepatitis C Virus Downregulates Ubiquitin-Conjugating Enzyme E2S Expression To Prevent Proteasomal Degradation of NS5A, Leading to Host Cells More Sensitive to DNA Damage.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Ubiquitination dynamics in human tumour viruses: Viral infection, oncogenesis and antiviral therapy.The FEBS journal · 2026Review
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Decoding microbial carcinogenic strategies: ubiquitination and SUMO modification.Frontiers in microbiology · 2025Review
- Lipid droplets in pathogen infection and host immunity.Acta pharmacologica Sinica · 2024Review
- CDK4/6 inhibitors downregulate the ubiquitin-conjugating enzymes UBE2C/S/T involved in the ubiquitin-proteasome pathway in ER + breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Dual-Role Ubiquitination Regulation Shuttling the Entire Life Cycle of the Flaviviridae.Frontiers in microbiology · 2022Review
- Adenosylhomocysteinase like 1 interacts with nonstructural 5A and regulates hepatitis C virus propagation.Journal of microbiology (Seoul, Korea) · 2021Article
- A New Twist in Protein Kinase B/Akt Signaling: Role of Altered Cancer Cell Metabolism in Akt-Mediated Therapy Resistance.International journal of molecular sciences · 2020Review
- E2 ubiquitin-conjugating enzyme UBE2L6 promotes Senecavirus A proliferation by stabilizing the viral RNA polymerase.PLoS pathogens · 2020Article
- Cortactin Interacts with Hepatitis C Virus Core and NS5A Proteins: Implications for Virion Assembly.Journal of virology · 2020Article
- Nonstructural NS5A Protein Regulates LIM and SH3 Domain Protein 1 to Promote Hepatitis C Virus Propagation.Molecules and cells · 2020Article
- PACSIN2 Interacts with Nonstructural Protein 5A and Regulates Hepatitis C Virus Assembly.Journal of virology · 2020Article
- Hepatitis C Virus NS3 Protein Plays a Dual Role in WRN-Mediated Repair of Nonhomologous End Joining.Journal of virology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) infection may cause chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV exploits cellular machineries to establish persistent infection. We demonstrate here that ubiquitin-conjugating enzyme E2S (UBE2S), a member of the ubiquitin-conjugating enzyme family (E2s), was downregulated by endoplasmic reticulum stress caused by HCV in Huh7 cells. UBE2S interacted with domain I of HCV NS5A and degraded NS5A protein through the Lys11-linked proteasome-dependent pathway. Overexpression of UBE2S suppressed viral propagation, while depletion of UBE2S expression increased viral infectivity. Enzymatically inactive UBE2S C95A mutant exerted no antiviral activity, suggesting that ubiquitin-conjugating enzymatic activity was required for the suppressive role of UBE2S. Chromatin ubiquitination plays a crucial role in the DNA damage response. We showed that the levels of UBE2S and Lys11 chains bound to the chromatin were markedly decreased in the context of HCV replication, rendering HCV-infected cells more sensitive to DNA damage. These data suggest that HCV counteracts antiviral activity of UBE2S to optimize viral propagation and may contribute to HCV-induced liver pathogenesis.
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Registered trials
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.