ArticlePloS one2017
The effect of Ingenol-B on the suppressive capacity of elite suppressor HIV-specific CD8+ T cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Disruption of latent HIV in vivo during the clearance of actinic keratosis by ingenol mebutate.JCI insight · 2019Trial
- Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells.Nature immunology · 2024Article
- Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects.Pathogens (Basel, Switzerland) · 2022Article
- TCR-mimic bispecific antibodies to target the HIV-1 reservoir.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The ingenol-based protein kinase C agonist GSK445A is a potent inducer of HIV and SIV RNA transcription.PLoS pathogens · 2022Article
- A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or Prevent COVID-19 Mortality.Pharmaceutical research · 2020Article
- Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents.Microorganisms · 2020Review
- Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8Journal of virology · 2019Article
- Broad-Spectrum and Personalized Guide RNAs for CRISPR/Cas9 HIV-1 Therapeutics.AIDS research and human retroviruses · 2018Article
- Targeting the Latent Reservoir for HIV-1.Immunity · 2018Review
- Review
- Novel Latency Reversal Agents for HIV-1 Cure.Annual review of medicine · 2018Review
- Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSome latency-reversing agents (LRAs) inhibit HIV-specific CD8+ T cell responses. In a prior study of protein kinase C (PKC) agonists, we found that bryostatin-1 inhibited elite controller/suppressor (ES) CD8+ T cell suppressive activity whereas prostratin had no effect. Ingenol-B is another PKC agonist with potent LRA activity both by itself and in combination with the bromodomain inhibitor JQ1; however its effect on CD8+ T cell mediated control of HIV-1 replication is unknown.
methodsCD8+ T cells were isolated from ES and treated with bryostatin-1, prostratin, ingenol-B, and JQ1 as well as a combination of each PKC-agonist with JQ1. The cells were then tested in the viral suppression assay. To assess possible mechanisms of inhibition, CD8+ T cells were treated with the LRAs and analyzed for the expression of various immune cell markers.
resultsIngenol-B had no effect on the ability of ES CD8+ T cells to suppress viral replication, however, the combination of ingenol-B and JQ1 caused a modest, but significant decrease in this suppressive capacity. The mechanism of the inhibitory effect of the JQ1 and ingenol-B combination relative to ingenol-B alone was unclear but the effect appeared to be dose dependent.
conclusionsIngenol-B does not inhibit HIV-specific CD8+ T cell responses in vitro. These responses are however modestly inhibited when 100 nMingenol-B is combined with JQ1. Since HIV-specific CD8+ T cell activity may be essential for the eradication of reactivated latently infected cells, the potency of latency-reversal activity of drug combinations must be balanced against the effects of the combinations on HIV-specific CD8+ T cell responses.
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