ArticleEmerging microbes & infections2018
TSC1 and DEPDC5 regulate HIV-1 latency through the mTOR signaling pathway.
Article in Emerging microbes & infections, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- COG6 is an essential host factor for influenza A virus infection.Microbiology spectrum · 2025Article
- Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- HIV Reservoirs and Treatment Strategies toward Curing HIV Infection.International journal of molecular sciences · 2024Review
- PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?The international journal of neuropsychopharmacology · 2024Review
- High-throughput CRISPR technology: a novel horizon for solid organ transplantation.Frontiers in immunology · 2023Review
- Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.Journal of oncology · 2023Review
- Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.The Journal of clinical investigation · 2022Article
- HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency.Frontiers in cellular and infection microbiology · 2022Review
- U1 and OM10.1. Myeloid Cell Lines as Surrogate Models of Reversible Proviral Latency.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Targeting and Understanding HIV Latency: The CRISPR System against the Provirus.Pathogens (Basel, Switzerland) · 2021Review
- Review
- CAGE-seq reveals that HIV-1 latent infection does not trigger unique cellular responses in a Jurkat T cell model.Journal of virology · 2021Article
- Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing ActivityJournal of virology · 2021Article
- A Review of Current Strategies Towards the Elimination of Latent HIV-1 and Subsequent HIV-1 Cure.Current HIV research · 2021Article
- Block-And-Lock: New Horizons for a Cure for HIV-1.Viruses · 2020Review
- PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-κB signaling.EMBO reports · 2020Article
- Article
- Modulation of mTORC1 Signaling Pathway by HIV-1.Cells · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The latent reservoir of HIV-1 presents a major barrier to viral eradication. The mechanism of the establishment and maintenance of the latent viral reservoir is not yet fully understood, which hinders the development of effective curative strategies. In this study, we identified two inhibitory genes, TSC1 and DEPDC5, that maintained HIV-1 latency by suppressing the mTORC1 pathway. We first adapted a genome-wide CRISPR screening approach to identify host factors required for HIV latency in a T-cell-based latency model and discovered two inhibitory genes, TSC1 and DEPDC5, which are potentially involved in HIV-1 latency. Knockout of either TSC1 or DEPDC5 led to enhanced HIV-1 reactivation in both a T-cell line (C11) and a monocyte cell line (U1), and this enhancement could be antagonized by the mTORC1 inhibitor rapamycin. Further evaluation of the mechanism revealed that TSC1 suppresses AKT-mTORC1-S6 via downregulation of Rheb, whereas DEPDC5 inhibits AKT-mTORC1-S6 through RagA. Overall, both TSC1 and DEPDC5 negatively regulate the AKT-mTORC1 pathway, and thus their agonists could be used in the development of new therapeutic approaches for activating HIV-1 latency.
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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.