ArticleRetrovirology2016
Janus kinase inhibition suppresses PKC-induced cytokine release without affecting HIV-1 latency reversal ex vivo.
Article in Retrovirology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Activating PKC-ε induces HIV expression with improved tolerability.PLoS pathogens · 2025Article
- Single-molecule RNA-FISH analysis reveals stochasticity in reactivation of latent HIV-1 regulated by Nuclear Orphan Receptors NR4A and cMYC.Research square · 2024Article
- New Concepts in Therapeutic Manipulation of HIV-1 Transcription and Latency: Latency Reversal versus Latency Prevention.Viruses · 2023Review
- Clearance of HIV-1 or SIV reservoirs by promotion of apoptosis and inhibition of autophagy: Targeting intracellular molecules in cure-directed strategies.Journal of leukocyte biology · 2022Review
- New Applications of JAK/STAT Inhibitors in Pediatrics: Current Use of Ruxolitinib.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Histone deacetylase inhibition reduces deleterious cytokine release induced by ingenol stimulation.Biochemical pharmacology · 2022Article
- Latency Reversal 2.0: Giving the Immune System a Seat at the Table.Current HIV/AIDS reports · 2021Review
- The Interplay of HIV-1 and Macrophages in Viral Persistence.Frontiers in microbiology · 2021Review
- Mechanistic differences underlying HIV latency in the gut and blood contribute to differential responses to latency-reversing agents.AIDS (London, England) · 2020Article
- The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19.Cytokine & growth factor reviews · 2020Review
- Structure-Activity Relationship Analysis of Benzotriazine Analogues as HIV-1 Latency-Reversing Agents.Antimicrobial agents and chemotherapy · 2020Article
- Senotherapeutics and HIV-1 Persistence.Current HIV/AIDS reports · 2020Review
- Prodrugs of PKC modulators show enhanced HIV latency reversal and an expanded therapeutic window.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Latency reversal agents modulate HIV antigen processing and presentation to CD8 T cells.PLoS pathogens · 2020Article
- Nuclear Transit and HIV LTR Binding of NF-κB Subunits Held by IκB Proteins: Implications for HIV-1 Activation.Viruses · 2019Article
- Type I interferon signaling, regulation and gene stimulation in chronic virus infection.Seminars in immunology · 2019Review
- CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention.Frontiers in cell and developmental biology · 2019Review
- Synthetic Ingenols Maximize Protein Kinase C-Induced HIV-1 Latency Reversal.Antimicrobial agents and chemotherapy · 2018Article
- IL-15 regulates susceptibility of CD4Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained and Reversed.Journal of virology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDespite the durable viral suppression afforded by antiretroviral therapy, HIV-1 eradication will require strategies to target latently infected cells that persist in infected individuals. Protein kinase C (PKC) activation is a promising strategy to reactivate latent proviruses and allow for subsequent recognition and clearance of infected cells by the immune system. Ingenol derivatives are PKC agonists that induce latency reversal but also lead to T cell activation and the release of pro-inflammatory cytokines, which would be undesirable in vivo. In this work, we sought to identify compounds that would suppress pro-inflammatory cytokine production in the context of PKC activation. DESIGN AND
methodsWe performed an in vitro screen to identify compounds that could dampen pro-inflammatory cytokine release associated with T cell activation, using IL-6 as a model cytokine. We then tested the ability of the most promising screening hit, the FDA-approved Janus Kinase (JAK) inhibitor ruxolitinib, to diminish release of multiple cytokines and its effect on latency reversal using cells from HIV-1-positive, aviremic participants.
resultsWe demonstrate that co-administration of ruxolitinib with ingenol-3,20-dibenzoate significantly reduces pro-inflammatory cytokine release without impairing latency reversal ex vivo.
conclusionThe combination of ingenol compounds and JAK inhibition represents a novel strategy for HIV-1 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.