ArticleJournal of virology2019
Hepatitis C Virus Infection Is Inhibited by a Noncanonical Antiviral Signaling Pathway Targeted by NS3-NS4A.
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 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Hijacking Host Communication: The Central Role of Extracellular Vesicles in Infectious Disease Pathogenesis.Cells · 2026Review
- The RIG-I-like receptor family of immune proteins.Molecular cell · 2025Review
- Reconstitution of interferon regulatory factor 7 expression restores interferon beta induction in Huh7 cells.Journal of virology · 2025Article
- Synthetic RIG-I-Agonist RNA Induces Death of Hepatocellular Carcinoma Cells.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Genetic reinstatement of RIG-I in chickens reveals insights into avian immune evolution and influenza interaction.Frontiers in immunology · 2025Article
- From viruses to cancer: exploring the role of the hepatitis C virus NS3 protein in carcinogenesis.Infectious agents and cancer · 2024Review
- Hepatitis C Virus and the Host: A Mutual Endurance Leaving Indelible Scars in the Host's Immunity.International journal of molecular sciences · 2023Review
- Riplet Binds the Zinc Finger Antiviral Protein (ZAP) and Augments ZAP-Mediated Restriction of HIV-1.Journal of virology · 2022Article
- Review
- Signaling from the RNA sensor RIG-I is regulated by ufmylation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Viruses utilize ubiquitination systems to escape TLR/RLR-mediated innate immunity.Frontiers in immunology · 2022Review
- Review
- N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages.PLoS pathogens · 2021Article
- Immune system control of hepatitis C virus infection.Current opinion in virology · 2021Review
- Host Innate Immunity Against Hepatitis Viruses and Viral Immune Evasion.Frontiers in microbiology · 2021Review
- Running With Scissors: Evolutionary Conflicts Between Viral Proteases and the Host Immune System.Frontiers in immunology · 2021Review
- Potential for Protein Kinase Pharmacological Regulation inInternational journal of molecular sciences · 2020Review
- RIG-I-like receptors: their regulation and roles in RNA sensing.Nature reviews. Immunology · 2020Review
- Review
- Hepatitis C Virus: Evading the Intracellular Innate Immunity.Journal of clinical medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The hepatitis C virus (HCV) NS3-NS4A protease complex is required for viral replication and is the major viral innate immune evasion factor. NS3-NS4A evades antiviral innate immunity by inactivating several proteins, including MAVS, the signaling adaptor for RIG-I and MDA5, and Riplet, an E3 ubiquitin ligase that activates RIG-I. Here, we identified a Tyr-16-Phe (Y16F) change in the NS4A transmembrane domain that prevents NS3-NS4A targeting of Riplet but not MAVS. This Y16F substitution reduces HCV replication in Huh7 cells, but not in Huh-7.5 cells, known to lack RIG-I signaling. Surprisingly, deletion of RIG-I in Huh7 cells did not restore Y16F viral replication. Rather, we found that Huh-7.5 cells lack Riplet expression and that the addition of Riplet to these cells reduced HCV Y16F replication, whereas the addition of Riplet lacking the RING domain restored HCV Y16F replication. In addition, TBK1 inhibition or IRF3 deletion in Huh7 cells was sufficient to restore HCV Y16F replication, and the Y16F protease lacked the ability to prevent IRF3 activation or interferon induction. Taken together, these data reveal that the NS4A Y16 residue regulates a noncanonical Riplet-TBK1-IRF3-dependent, but RIG-I-MAVS-independent, signaling pathway that limits HCV infection.
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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.