ArticleJournal of virology2020
ISGylation of Hepatitis C Virus NS5A Protein Promotes Viral RNA Replication via Recruitment of Cyclophilin A.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Herpesviruses hijack ISGylation to promote viral capsid assembly.Science advances · 2026Article
- PARP3 Promotes SARS-CoV-2 Replication via Interaction with the Viral Nucleocapsid Protein.The Kobe journal of medical sciences · 2026Article
- A tale of dual role: HECT‑type E3 ubiquitin ligase mechanisms in liver diseases (Review).International journal of molecular medicine · 2026Review
- The roles of post-translational modifications in the pathogenesis of RNA viruses: allies or adversaries?Frontiers in microbiology · 2026Review
- Unraveling the Biology of Interferon-Stimulated Genes: Mechanisms, Functions, and Clinical Implications.Infection and drug resistance · 2026Review
- Hepatitis C Virus NS5A Inhibits YAP1-HSC70 Interaction, Thereby Preventing YAP1 Degradation Via Chaperone-Mediated Autophagy.The Kobe journal of medical sciences · 2025Article
- A Quinoline Derivative HZ-6d Induces Antiviral Activity Against Hepatitis C Virus Via Apoptosis-Mediated Cytotoxicity.The Kobe journal of medical sciences · 2025Article
- Porcine reproductive and respiratory syndrome virus NSP5 exploited UBE2L6 to promote viral replication via antagonising host RLRs and ISGylation.Veterinary research · 2025Article
- NSUN2-mediated HCV RNA m5C Methylation Facilitates Viral RNA Stability and Replication.Genomics, proteomics & bioinformatics · 2025Article
- Comprehensive profiling of host- and virus-derived circular RNAs during vesicular stomatitis virus infection.Frontiers in cellular and infection microbiology · 2025Article
- SARS-CoV-2 papain-like protease inhibits ISGylation of the viral nucleocapsid protein to evade host anti-viral immunity.Journal of virology · 2024Article
- Unveiling the Multifaceted Roles of ISG15: From Immunomodulation to Therapeutic Frontiers.Vaccines · 2024Review
- Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.Viruses · 2023Article
- Interferon-stimulated gene 15 facilitates BTV replication through interacting with the NS1 protein.Frontiers in microbiology · 2023Article
- UFL1 promotes antiviral immune response by maintaining STING stability independent of UFMylation.Cell death and differentiation · 2023Article
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents.Drug discovery today · 2022Review
- Dual-Role Ubiquitination Regulation Shuttling the Entire Life Cycle of the Flaviviridae.Frontiers in microbiology · 2022Review
- NS5A-ISGylation via Lysine 26 Has a Critical Role for Efficient Propagation of Hepatitis C Virus Genotype 2a.The Kobe journal of medical sciences · 2021Article
- HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response.Viruses · 2021Review
- The Role of Chaperone-Mediated Autophagy in Hepatitis C Virus-Induced Pathogenesis.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is covalently conjugated to many substrate proteins in order to modulate their functions; this conjugation is called ISGylation. Several groups reported that the ISGylation of hepatitis C virus (HCV) NS5A protein affects HCV replication. However, the ISG15 conjugation sites on NS5A are not well determined, and it is unclear whether the role of NS5A ISGylation in HCV replication is proviral or antiviral. Here, we investigated the role of NS5A ISGylation in HCV replication by using HCV RNA replicons that encode a mutation at each lysine (Lys) residue of the NS5A protein. Immunoblot analyses revealed that 5 Lys residues (K44, K68, K166, K215, and K308) of the 14 Lys residues within NS5A (genotype 1b, Con1) have the potential to accept ISGylation. We tested the NS5A ISGylation among different HCV genotypes and observed that the NS5A proteins of all of the HCV genotypes accept ISGylation at multiple Lys residues. Using an HCV luciferase reporter replicon assay revealed that residue K308 of NS5A is important for HCV (1b, Con1) RNA replication. We observed that K308, one of the Lys residues for NS5A ISGylation, is located within the binding region of cyclophilin A (CypA), which is the critical host factor for HCV replication. We obtained evidence derived from all of the HCV genotypes suggesting that NS5A ISGylation enhances the interaction between NS5A and CypA. Taken together, these results suggest that NS5A ISGylation functions as a proviral factor and promotes HCV replication via the recruitment of CypA.
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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.