ArticleVirology journal2011
Inhibition of cyclophilins alters lipid trafficking and blocks hepatitis C virus secretion.
Article in Virology journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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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
20 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.Viruses · 2023Article
- Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches.Pathogens (Basel, Switzerland) · 2021Review
- Article
- Differences across cyclophilin A orthologs contribute to the host range restriction of hepatitis C virus.eLife · 2019Article
- Modulation of Lipid Droplet Metabolism-A Potential Target for Therapeutic Intervention inFrontiers in microbiology · 2017Review
- Article
- Chaperones in hepatitis C virus infection.World journal of hepatology · 2016Review
- Review
- The role of immunophilins in viral infection.Biochimica et biophysica acta · 2015Article
- A Proline-Tryptophan Turn in the Intrinsically Disordered Domain 2 of NS5A Protein Is Essential for Hepatitis C Virus RNA Replication.The Journal of biological chemistry · 2015Article
- Alisporivir inhibition of hepatocyte cyclophilins reduces HBV replication and hepatitis B surface antigen production.Gastroenterology · 2015Article
- The Hsp90 cochaperones Cpr6, Cpr7, and Cns1 interact with the intact ribosome.Eukaryotic cell · 2015Article
- Hepatocyte nuclear factor 4α and downstream secreted phospholipase A2 GXIIB regulate production of infectious hepatitis C virus.Journal of virology · 2014Article
- Curing a viral infection by targeting the host: the example of cyclophilin inhibitors.Antiviral research · 2013Review
- Hepatitis C virus, cholesterol and lipoproteins--impact for the viral life cycle and pathogenesis of liver disease.Viruses · 2013Review
- Lipids and HCV.Seminars in immunopathology · 2013Review
- Suppression of viral RNA binding and the assembly of infectious hepatitis C virus particles in vitro by cyclophilin inhibitors.Journal of virology · 2012Article
- Cyclophilin involvement in the replication of hepatitis C virus and other viruses.Biological chemistry · 2012Review
- Exploitation of lipid components by viral and host proteins for hepatitis C virus infection.Frontiers in microbiology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Host cyclophilin (cyp) inhibitors, such as NIM811, efficiently inhibit replication of hepatitis C virus (HCV) and have shown significant promise in recent clinical trials for the treatment of chronic HCV. It is therefore important to fully understand the mechanism of action of these therapeutic agents. Data obtained from comprehensive systems biology approaches have led to the hypothesis that the antiviral activity of cyclophilin inhibitors is mediated through impairing the cellular machinery on which HCV relies to traffic cofactors necessary for formation of the replication complex. Indeed, our results demonstrate when cyclophilins are inhibited by NIM811, lipid and protein trafficking within the VLDL pathway is impaired. Following treatment of replicon or HCV infected cells with NIM811, intracellular lipid droplets (LD) more than double in size and decrease in number. Changes in the LDs in response to cyclophilin inhibition are dependent upon expression of viral proteins. Additionally, in cells treated with NIM811, apoB accumulates in a crescent or ring shaped structure surrounding the enlarged LDs and is no longer secreted. Silencing of cypA or cyp40 using siRNA had a similar effect on LD size and apoB localization as compound treatment, suggesting these cyclophilins may play an important role in lipid and apoB trafficking. Interestingly, the decrease in apoB secretion correlates with a decrease in release of viral particles in HCV infected cells. Altogether, these results add a new level of complexity to the mechanism of action of cyclophilin inhibition, and suggest the role for cyclophilins in the virus life cycle extends beyond replication to virus release.
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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.