ArticleGut2016
Host cell mTORC1 is required for HCV RNA replication.
Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval.Drug design, development and therapy · 2022Pooled it
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- The Efficient Antiviral Response of A549 Cells Is Enhanced When Mitochondrial Respiration Is Promoted.Pathogens (Basel, Switzerland) · 2022Article
- Review
- Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches.Journal of biomolecular structure & dynamics · 2022Article
- Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Occult Infection with Hepatitis C Virus: Looking for Clear-Cut Boundaries and Methodological Consensus.Journal of clinical medicine · 2021Review
- Dentistry pathways of coronaviruses transmission: a review.Virusdisease · 2021Review
- mTORC2 confers neuroprotection and potentiates immunity during virus infection.Nature communications · 2021Article
- Cellular factors involved in the hepatitis C virus life cycle.World journal of gastroenterology · 2021Review
- Initial HCV infection of adult hepatocytes triggers a temporally structured transcriptional program containing diverse pro- and anti-viral elements.Journal of virology · 2021Article
- Hedgehog Signaling: Implications in Cancers and Viral Infections.International journal of molecular sciences · 2021Review
- Dengue Virus Dysregulates Master Transcription Factors and PI3K/AKT/mTOR Signaling Pathway in Megakaryocytes.Frontiers in cellular and infection microbiology · 2021Article
- Interaction of Severe Acute Respiratory Syndrome Coronavirus 2 and Diabetes.Frontiers in endocrinology · 2021Review
- COVID-19 and diabetes mellitus: how one pandemic worsens the other.Reviews in endocrine & metabolic disorders · 2020Review
- Mechanistic Target of Rapamycin Signaling Activation Antagonizes Autophagy To Facilitate Zika Virus Replication.Journal of virology · 2020Article
- Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review.Viruses · 2020Review
- microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and de novo Lipogenesis.Viruses · 2020Article
- Host-Directed Antiviral Therapy.Clinical microbiology reviews · 2020Review
- Drug repurposing against COVID-19: focus on anticancer agents.Journal of experimental & clinical cancer research : CR · 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
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveChronically HCV-infected orthotopic liver transplantation (OLT) recipients appear to have improved outcomes when their immunosuppressive regimen includes a mammalian target of rapamycin (mTOR) inhibitor. The mechanism underlying this observation is unknown.
designWe used virological assays to investigate mTOR signalling on the HCV replication cycle. Furthermore, we analysed HCV RNA levels of 42 HCV-positive transplanted patients treated with an mTOR inhibitor as part of their immunosuppressive regimen.
resultsThe mTOR inhibitor rapamycin was found to be a potent inhibitor for HCV RNA replication in Huh-7.5 cells as well as primary human hepatocytes. Half-maximal inhibition was observed at 0.01 µg/mL, a concentration that is in the range of serum levels seen in transplant recipients and does not affect cell proliferation. Early replication cycle steps such as cell entry and RNA translation were not affected. Knockdown of raptor, an essential component of mTORC1, but not rictor, an essential component of mTORC2, inhibited viral RNA replication. In addition, overexpression of raptor led to higher viral RNA replication, demonstrating that mTORC1, but not mTORC2, is required for HCV RNA replication. In 42 HCV-infected liver-transplanted or kidney-transplanted patients who were switched to an mTOR inhibitor, we could verify that mTOR inhibition decreased HCV RNA levels in vivo.
conclusionsOur data identify mTORC1 as a novel HCV replication factor. These findings suggest an underlying mechanism for the observed benefits of mTOR inhibition in HCV-positive OLT recipients and potentiate further investigation of mTOR-containing regimens in HCV-positive recipients of solid organ transplants.
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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.