ArticleProceedings of the National Academy of Sciences of the United States of America2015
Targeting of mTOR catalytic site inhibits multiple steps of the HIV-1 lifecycle and suppresses HIV-1 viremia in humanized mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 101 citations in OpenAlex.
- Review
- Metabolic reprogramming of CD4⁺ T cells by Zaprinast induces HIV-1 latency reversal ex vivo.Retrovirology · 2026Article
- Trackable Tolerogenic Macrophages Integrate PD-L1 and Rapamycin Signaling to Suppress Alloimmune Responses in Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Immuno-cell metabolic changes in HIV-1 infection.Infectious diseases & immunity · 2025Review
- Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.Cell reports. Medicine · 2024Article
- Metformin facilitates viral reservoir reactivation and their recognition by anti-HIV-1 envelope antibodies.iScience · 2024Article
- Mechanisms and efficacy of small molecule latency-promoting agents to inhibit HIV reactivation ex vivo.JCI insight · 2024Article
- Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms.Cell reports · 2024Article
- Comparative analysis of within-host dynamics of acute infection and viral rebound dynamics in postnatally SHIV-infected ART-treated infant rhesus macaques.bioRxiv : the preprint server for biology · 2024Article
- Metformin Enhances Antibody-Mediated Recognition of HIV-Infected CD4bioRxiv : the preprint server for biology · 2024Article
- Microglial- neuronal crosstalk in chronic viral infection through mTOR, SPP1/OPN and inflammasome pathway signaling.Frontiers in immunology · 2024Review
- Nucleoside Analog 2',3'-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1.Pharmaceutics · 2023Article
- Human immunodeficiency virus and antiretroviral therapy-mediated immune cell metabolic dysregulation in children born to HIV-infected women: potential clinical implications.Frontiers in immunology · 2023Review
- Evaluation and mechanism study of Pien Tze Huang against EV-A71 infection.Frontiers in pharmacology · 2023Article
- mTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses.Communications biology · 2022Article
- Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.The Journal of clinical investigation · 2022Article
- Engineered Zinc Finger Protein Targeting 2LTR Inhibits HIV Integration in Hematopoietic Stem and Progenitor Cell-Derived Macrophages: In Vitro Study.International journal of molecular sciences · 2022Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV necessitates host factors for successful completion of its life cycle. Mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that forms two complexes, mTORC1 and mTORC2. Rapamycin is an allosteric inhibitor of mTOR that selectively inhibits mTORC1. Rapamycin interferes with viral entry of CCR5 (R5)-tropic HIV and with basal transcription of the HIV LTR, potently inhibiting replication of R5 HIV but not CXCR4 (X4)-tropic HIV in primary cells. The recently developed ATP-competitive mTOR kinase inhibitors (TOR-KIs) inhibit both mTORC1 and mTORC2. Using INK128 as a prototype TOR-KI, we demonstrate potent inhibition of both R5 and X4 HIV in primary lymphocytes (EC50 < 50 nM), in the absence of toxicity. INK128 inhibited R5 HIV entry by reducing CCR5 levels. INK128 also inhibited both basal and induced transcription of HIV genes, consistent with inhibition of mTORC2, whose activity is critical for phosphorylation of PKC isoforms and, in turn, induction of NF-κB. INK128 enhanced the antiviral potency of the CCR5 antagonist maraviroc, and had favorable antiviral interactions with HIV inhibitors of reverse transcriptase, integrase and protease. In humanized mice, INK128 decreased plasma HIV RNA by >2 log10 units and partially restored CD4/CD8 cell ratios. Targeting of cellular mTOR with INK128 (and perhaps others TOR-KIs) provides a potential strategy to inhibit HIV, especially in patients with drug resistant HIV strains.
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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.