ArticlePLoS pathogens2017
In vivo activation of latent HIV with a synthetic bryostatin analog effects both latent cell "kick" and "kill" in strategy for virus eradication.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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.
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Who cites it
66 citing papers in PubMed, 94 citations in OpenAlex.
- Disruption of latent HIV in vivo during the clearance of actinic keratosis by ingenol mebutate.JCI insight · 2019Trial
- PKC inhibitors reveal PKC isoforms involved in HIV latency reversal and immunomodulation.Journal of virology · 2026Article
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Review
- Effects and mechanisms of monoclonal and polyclonal human antibodies in protection of humanized mice from HIV-1 challenge.bioRxiv : the preprint server for biology · 2025Article
- Yoda1, a Piezo1 agonist, induced latent HIV reactivation associated with upregulation of CD3/TCR complex and HLA genes.Research square · 2025Article
- Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?Biomolecules · 2025Review
- Pan-caspase inhibitors induce secretion of HIV-1 latency reversal agent lymphotoxin-alpha from cytokine-primed NK cells.Cell death discovery · 2025Article
- Activating PKC-ε induces HIV expression with improved tolerability.PLoS pathogens · 2025Article
- Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.Science advances · 2025Article
- HIV-1 latency reversal agent boosting is not limited by opioid use.JCI insight · 2024Article
- Review
- Nanoparticle delivery of Tat synergizes with classical latency reversal agents to express HIV antigen targets.Antimicrobial agents and chemotherapy · 2024Article
- HIV-1 latency reversal agent boosting is not limited by opioid use.medRxiv : the preprint server for health sciences · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells.Pathogens & immunity · 2024Article
- Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure.Viruses · 2023Review
- Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection.Microorganisms · 2023Review
- Secreted factors induced by PKC modulators do not indirectly cause HIV latency reversal.Virology · 2023Article
- Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations.International journal of molecular sciences · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The ability of HIV to establish a long-lived latent infection within resting CD4+ T cells leads to persistence and episodic resupply of the virus in patients treated with antiretroviral therapy (ART), thereby preventing eradication of the disease. Protein kinase C (PKC) modulators such as bryostatin 1 can activate these latently infected cells, potentially leading to their elimination by virus-mediated cytopathic effects, the host's immune response and/or therapeutic strategies targeting cells actively expressing virus. While research in this area has focused heavily on naturally-occurring PKC modulators, their study has been hampered by their limited and variable availability, and equally significantly by sub-optimal activity and in vivo tolerability. Here we show that a designed, synthetically-accessible analog of bryostatin 1 is better-tolerated in vivo when compared with the naturally-occurring product and potently induces HIV expression from latency in humanized BLT mice, a proven and important model for studying HIV persistence and pathogenesis in vivo. Importantly, this induction of virus expression causes some of the newly HIV-expressing cells to die. Thus, designed, synthetically-accessible, tunable, and efficacious bryostatin analogs can mediate both a "kick" and "kill" response in latently-infected cells and exhibit improved tolerability, therefore showing unique promise as clinical adjuvants for HIV eradication.
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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.