ArticleJournal of virology2012
Combination of biological screening in a cellular model of viral latency and virtual screening identifies novel compounds that reactivate HIV-1.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Mitotic deacetylase complex (MiDAC) recognizes the HIV-1 core promoter to control activated viral gene expression.PLoS pathogens · 2024Article
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
- Polyphenol Extracts from Grape Seeds and Apple Can Reactivate Latent HIV-1 Transcription through Promoting P-TEFb Release from 7SK snRNP.Disease markers · 2022Article
- Diversity of small molecule HIV-1 latency reversing agents identified in low- and high-throughput small molecule screens.Medicinal research reviews · 2020Review
- Novel Histone Deacetylase Inhibitors and HIV-1 Latency-Reversing Agents Identified by Large-Scale Virtual Screening.Frontiers in pharmacology · 2020Article
- Impact of Myeloid Reservoirs in HIV Cure Trials.Current HIV/AIDS reports · 2019Review
- Identification of Novel HIV-1 Latency-Reversing Agents from a Library of Marine Natural Products.Viruses · 2018Article
- A New Quinoline BRD4 Inhibitor Targets a Distinct Latent HIV-1 Reservoir for Reactivation from Other "Shock" Drugs.Journal of virology · 2018Article
- Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy.Molecules (Basel, Switzerland) · 2017Article
- Quantitation of Productively Infected Monocytes and Macrophages of Simian Immunodeficiency Virus-Infected Macaques.Journal of virology · 2016Article
- Molecular mechanisms of HIV latency.The Journal of clinical investigation · 2016Review
- Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations.The Journal of clinical investigation · 2015Article
- The impact of the HIRA histone chaperone upon global nucleosome architecture.Cell cycle (Georgetown, Tex.) · 2015Article
- Review
- Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART.Gene therapy · 2013Review
- HIV-1 transcription and latency: an update.Retrovirology · 2013Review
- Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs.Lancet (London, England) · 2013Review
- Histone deacetylase inhibitors (HDACis) that release the positive transcription elongation factor b (P-TEFb) from its inhibitory complex also activate HIV transcription.The Journal of biological chemistry · 2013Article
- Combined approaches for HIV cure.Current opinion in HIV and AIDS · 2013Review
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 2 countries.
Funding
Abstract
Although highly active antiretroviral therapy (HAART) has converted HIV into a chronic disease, a reservoir of HIV latently infected resting T cells prevents the eradication of the virus from patients. To achieve eradication, HAART must be combined with drugs that reactivate the dormant viruses. We examined this problem in an established model of HIV postintegration latency by screening a library of small molecules. Initially, we identified eight molecules that reactivated latent HIV. Using them as templates, additional hits were identified by means of similarity-based virtual screening. One of those hits, 8-methoxy-6-methylquinolin-4-ol (MMQO), proved to be useful to reactivate HIV-1 in different cellular models, especially in combination with other known reactivating agents, without causing T-cell activation and with lower toxicity than that of the initial hits. Interestingly, we have established that MMQO produces Jun N-terminal protein kinase (JNK) activation and enhances the T-cell receptor (TCR)/CD3 stimulation of HIV-1 reactivation from latency but inhibits CD3-induced interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α) gene transcription. Moreover, MMQO prevents TCR-induced cell cycle progression and proliferation in primary T cells. The present study documents that the combination of biological screening in a cellular model of viral latency with virtual screening is useful for the identification of novel agents able to reactivate HIV-1. Moreover, we set the bases for a hypothetical therapy to reactivate latent HIV by combining MMQO with physiological or pharmacological TCR/CD3 stimulation.
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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.