ArticleJournal of hepatology2013
HCV NS5A and IRF9 compete for CypA binding.
Article in Journal of hepatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
17 citing papers in PubMed.
- Single-cell analysis reveals the regulatory role of ECT2 in HPV-driven cervical carcinogenesis process.Infectious agents and cancer · 2025Article
- Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers.Molecules (Basel, Switzerland) · 2024Review
- The Cyclophilin Inhibitor Rencofilstat Decreases HCV-Induced Hepatocellular Carcinoma Independently of Its Antiviral Activity.Viruses · 2023Article
- African Swine Fever Virus MGF505-7R Interacts with Interferon Regulatory Factor 9 to Evade the Type I Interferon Signaling Pathway and Promote Viral Replication.Journal of virology · 2023Article
- Cyclophilin A Inhibits Human Respiratory Syncytial Virus (RSV) Replication by Binding to RSV-N through Its PPIase Activity.Journal of virology · 2021Article
- Advances in Foot-and-Mouth Disease Virus Proteins Regulating Host Innate Immunity.Frontiers in microbiology · 2020Review
- Interferon Regulatory Factor 9 Structure and Regulation.Frontiers in immunology · 2018Review
- Review
- Classical swine fever virus NS5A protein changed inflammatory cytokine secretion in porcine alveolar macrophages by inhibiting the NF-κB signaling pathway.Virology journal · 2016Article
- Functional differences in hepatitis C virus nonstructural (NS) 3/4A- and 5A-specific T cell responses.Scientific reports · 2016Article
- Chaperones in hepatitis C virus infection.World journal of hepatology · 2016Review
- Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9.Virology · 2015Article
- Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection.Chemistry & biology · 2015Article
- Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors.Gastroenterology · 2014Article
- Cyclophilins as modulators of viral replication.Viruses · 2013Review
- Profile of alisporivir and its potential in the treatment of hepatitis C.Drug design, development and therapy · 2013Review
- Opportunities and Risks of Host-targeting Antiviral Strategies for Hepatitis C.Current hepatitis reports · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
BACKGROUND &
aimsCyclophilin A (CypA) is vital for HCV replication. Cyp inhibitors successfully decrease viral loads in HCV-infected patients. However, their mechanisms of action remain unknown. Since interferon (IFN) can also suppress HCV replication, we asked whether a link between CypA and the IFN response exists.
methodsWe used cellular and recombinant pulldown approaches to investigate the possibility of a specific association of CypA with host ligands.
resultsWe found for the first time that CypA binds to a major component of the IFN response - the IFN regulatory factor 9 (IRF9). IRF9 is the DNA-binding component of the transcriptional IFN-stimulated gene factor 3 (ISGF3). CypA binds directly to IRF9 via its peptidyl-prolyl isomerase (PPIase) pocket. Cyp inhibitors such as cyclosporine A (CsA) or non-immunosuppressive derivates such as alisporivir and SCY-635, prevent IRF9-CypA complex formation. CypA binds to the C-terminal IRF-association-domain (IAD), but not to the DNA-binding or linker domains of IRF9. Remarkably, CypA associates with the multimeric ISGF3 complex. We also obtained evidence that CypA neutralization enhances IFN-induced transcription. Interestingly, the hepatitis C virus (HCV) non-structural 5A (NS5A) protein, which is known to modulate the IFN response, competes with IRF9 for CypA binding and can prevent the formation of IRF9-CypA complexes.
conclusionsThis study demonstrates for the first time that CypA binds specifically to a component of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, IRF9. This study also reveals a novel opportunity of HCV to modulate the IFN response via NS5A.
Indexed as
Identifiers
What OpenQuestion holds
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.