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Updated: May 23, 2026

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Protein Kinase C: One Pathway towards the Eradication of Latent HIV-1 Reservoirs
Lisa N McKernan1, David Momjian, Joseph Kulkosky
1Department of Biology, Chestnut Hill College, Philadelphia, PA 19118, USA.
Abstract:
An effective means to eradicate latent reservoirs in HIV-1-infected individuals remains elusive. Attempts to purge these reservoirs were undertaken over a decade ago without success. The subsequent lapse in further clinical attempts since may have been justified as our knowledge of the mechanisms which underpin the latent state still evolves. Although additional novel molecular antagonists of HIV-1 latency have subsequently been reported, these candidate agents have not been tested in human trials for reservoir ablation. This review provides an overview of the protein kinase C (PKC) pathway which can be modulated by small molecular agents to induce the expression of latent HIV-1 from within infected reservoir cells. Some of these agents have been tested against select cancers with seemingly tolerable side effects. As such, modulation of the PKC pathway may yet be a viable mechanism toward HIV-1 reservoir eradication.
Insights
Eradicating latent HIV-1 reservoirs is challenging. Modulating the protein kinase C (PKC) pathway with small molecules shows promise for reactivating latent HIV-1 and potentially eliminating reservoirs.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Effective strategies to eliminate latent Human Immunodeficiency Virus type 1 (HIV-1) reservoirs are currently lacking.
- Previous attempts at reservoir purging over a decade ago were unsuccessful, and research has since focused on understanding latency mechanisms.
- Novel molecular antagonists for HIV-1 latency exist but require human trials for reservoir ablation efficacy.
Purpose of the Study:
- To review the protein kinase C (PKC) pathway as a potential target for HIV-1 reservoir eradication.
- To explore small molecular agents that modulate the PKC pathway to induce latent HIV-1 expression.
Main Methods:
- Review of existing literature on the PKC pathway and its role in HIV-1 latency.
- Analysis of small molecular agents targeting the PKC pathway.
- Examination of preclinical and clinical data for PKC modulators.
Main Results:
- The protein kinase C (PKC) pathway can be modulated by small molecules to induce the expression of latent HIV-1.
- Some PKC-modulating agents have demonstrated tolerable side effects in cancer treatments.
- No PKC-targeting agents have yet been tested in human trials specifically for HIV-1 reservoir ablation.
Conclusions:
- Modulation of the PKC pathway represents a potential therapeutic strategy for HIV-1 reservoir eradication.
- Further clinical investigation of PKC pathway modulators is warranted for HIV-1 cure research.
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