ArticleMolecular therapy. Nucleic acids2015
Novel RNA Duplex Locks HIV-1 in a Latent State via Chromatin-mediated Transcriptional Silencing.
Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
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- World free HIV: the novel therapeutic approaches for eliminating latent HIV infection.Virology journal · 2026Review
- HIV associated immune aging among people living with HIV: implications for long-term antiretroviral therapy and potential HIV cure interventions in sub-Saharan Africa.Frontiers in immunology · 2026Review
- Epigenetic regulation of HIV-1 transcription: insights into latency mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.International journal of molecular sciences · 2025Article
- Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.Drug delivery and translational research · 2025Review
- FUBP3: A new player in HIV-1 transcriptional activation and immune regulation.Molecular therapy. Nucleic acids · 2025Article
- Breaking Barriers to an HIV-1 Cure: Innovations in Gene Editing, Immune Modulation, and Reservoir Eradication.Life (Basel, Switzerland) · 2025Review
- Current State of Therapeutics for HTLV-1.Viruses · 2024Review
- Mechanisms and efficacy of small molecule latency-promoting agents to inhibit HIV reactivation ex vivo.JCI insight · 2024Article
- MicroRNAs and long non-coding RNAs during transcriptional regulation and latency of HIV and HTLV.Retrovirology · 2024Review
- Advances in HIV Gene Therapy.International journal of molecular sciences · 2024Review
- A CRISPR Screen of HIV Dependency Factors Reveals ThatViruses · 2023Article
- A CRISPR screen of HIV dependency factors revealsbioRxiv : the preprint server for biology · 2023Article
- Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk.Frontiers in immunology · 2023Review
- Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.Molecules (Basel, Switzerland) · 2022Review
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
- Targeted Nanocarrier Delivery of RNA Therapeutics to Control HIV Infection.Pharmaceutics · 2022Review
- The reservoir of latent HIV.Frontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional gene silencing (TGS) of mammalian genes can be induced by short interfering RNA (siRNA) targeting promoter regions. We previously reported potent TGS of HIV-1 by siRNA (PromA), which targets tandem NF-κB motifs within the viral 5'LTR. In this study, we screened a siRNA panel with the aim of identifying novel 5'LTR targets, to provide multiplexing potential with enhanced viral silencing and application toward developing alternate therapeutic strategies. Systematic examination identified a novel siRNA target, si143, confirmed to induce TGS as the silencing mechanism. TGS was prolonged with virus suppression >12 days, despite a limited ability to induce post- TGS. Epigenetic changes associated with silencing were suggested by partial reversal by histone deacetylase inhibitors and confirmed by chromatin immunoprecipitation analyses, which showed induction of H3K27me3 and H3K9me3, reduction in H3K9Ac, and recruitment of argonaute-1, all characteristic marks of heterochromatin and TGS. Together, these epigenetic changes mimic those associated with HIV-1 latency. Further, robust resistance to reactivation was observed in the J-Lat 9.2 cell latency model, when transduced with shPromA and/or sh143. These data support si/shRNA-mediated TGS approaches to HIV-1 and provide alternate targets to pursue a functional cure, whereby the viral reservoir is locked in latency following antiretroviral therapy cessation.
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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.