ArticleThe Journal of biological chemistry2010
Hepatitis C virus NS5A activates the mammalian target of rapamycin (mTOR) pathway, contributing to cell survival by disrupting the interaction between FK506-binding protein 38 (FKBP38) and mTOR.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
- Virus infections and cancers: from mechanisms to therapeutics.Molecular biomedicine · 2026Review
- The emerging importance of immunophilins in fibrosis development.Molecular and cellular biochemistry · 2023Review
- Subversion of Host Innate Immunity byFrontiers in immunology · 2021Article
- Mechanistic Target of Rapamycin Signaling Activation Antagonizes Autophagy To Facilitate Zika Virus Replication.Journal of virology · 2020Article
- Review
- Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral Propagation.Scientific reports · 2018Article
- Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy.PloS one · 2018Article
- Functional evaluation of synthetic flavonoids and chalcones for potential antiviral and anticancer properties.Bioorganic & medicinal chemistry letters · 2017Article
- Article
- Review
- Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants.Clinical and experimental immunology · 2016Article
- Chaperones in hepatitis C virus infection.World journal of hepatology · 2016Review
- Post-transplantation malignancies: here today, gone tomorrow?Nature reviews. Clinical oncology · 2015Review
- West nile virus-induced activation of mammalian target of rapamycin complex 1 supports viral growth and viral protein expression.Journal of virology · 2014Article
- An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.PLoS pathogens · 2014Article
- mTOR in viral hepatitis and hepatocellular carcinoma: function and treatment.BioMed research international · 2014Review
- Hepatitis C virus infection: establishment of chronicity and liver disease progression.EXCLI journal · 2014Review
- Unfolded protein response in hepatitis C virus infection.Frontiers in microbiology · 2014Review
- FKBPs and the Akt/mTOR pathway.Cell cycle (Georgetown, Tex.) · 2013Article
- p53 controls hepatitis C virus non-structural protein 5A-mediated downregulation of GADD45α expression via the NF-κB and PI3K-Akt pathways.The Journal of general virology · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) often establishes a persistent infection that most likely involves a complex host-virus interplay. We previously reported that the HCV nonstructural protein 5A (NS5A) bound to cellular protein FKBP38 and resulted in apoptosis suppression in human hepatoma cell line Huh7. In the present research we further found that NS5A increased phosphorylation levels of two mTOR-targeted substrates, S6K1 and 4EBP1, in Huh7 in the absence of serum. mTOR inhibitor rapamycin or NS5A knockdown blocked S6K1 and 4EBP1 phosphorylation increase in NS5A-Huh7 and HCV replicon cells, suggesting that NS5A specifically regulated mTOR activation. Overexpression of NS5A and FKBP38 mutants or FKBP38 knockdown revealed this mTOR activation was dependent on NS5A-FKBP38 interaction. Phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 treatment in NS5A-Huh7 showed that the mTOR activation was independent of PI3K. Moreover, NS5A suppressed caspase 3 and poly(ADP-ribose) polymerase activation, which was abolished by NS5A knockdown or rapamycin, indicating NS5A inhibited apoptosis specifically through the mTOR pathway. Further analyses suggested that apoptotic inhibition exerted by NS5A via mTOR also required NS5A-FKBP38 interaction. Glutathione S-transferase pulldown and co-immunoprecipitation showed that NS5A disrupted the mTOR-FKBP38 association. Additionally, NS5A or FKBP38 mutants recovered the mTOR-FKBP38 interaction; this indicated that the impairment of mTOR-FKBP38 association was dependent on NS5A-FKBP38 binding. Collectively, our data demonstrate that HCV NS5A activates the mTOR pathway to inhibit apoptosis through impairing the interaction between mTOR and FKBP38, which may represent a pivotal mechanism for HCV persistence and pathogenesis.
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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.