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Updated: Mar 20, 2026
High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Preclinical shock strategies to reactivate latent HIV-1: an update
Gilles Darcis1, Benoît Van Driessche, Carine Van Lint
1aService of Molecular Virology, Département de Biologie Moléculaire (DBM), Université Libre de Bruxelles (ULB), Gosselies, BelgiumbService des Maladies Infectieuses, Université de Liège, Centre Hospitalier Universitaire (CHU) de Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
Purpose Of Review:
The 'shock and kill' strategy consists of activating HIV-1 expression to allow latently infected cells to die from viral cytopathic effects or host cytolytic immune effectors. This strategy relies on small molecules, called latency reversing agents, which activate HIV transcription.
Recent Findings:
Several mechanisms operating at the transcriptional level are involved in the establishment and maintenance of HIV-1 latency, including the absence of crucial inducible host transcription factors, epigenetic silencing, and the sequestration of the positive transcription elongation factor B. Progresses made toward the understanding of the molecular mechanisms of HIV-1 transcriptional repression have led to the identification of latency reversing agents that activate HIV transcription, such as histone deacetylase inhibitors or protein kinase C agonists. Multiple studies have recently pointed interesting ways to optimize the shock strategy by using combinations of latency reversing agents with an appropriate time schedule.
Summary:
Combining latency reversing agents appears as one potential strategy for therapy against HIV-1 latency.
Insights
The "shock and kill" approach aims to eliminate latent HIV-1 by reactivating the virus using latency reversing agents. Combining these agents shows promise for effective HIV therapy.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- HIV-1 latency establishes a persistent viral reservoir.
- Latent HIV-1 evades immune detection and current antiretroviral therapies.
- Reactivating latent HIV-1 is crucial for viral eradication strategies.
Purpose of the Study:
- To review the 'shock and kill' strategy for HIV-1 eradication.
- To explore the molecular mechanisms underlying HIV-1 latency.
- To discuss the potential of latency reversing agents (LRAs) in HIV therapy.
Main Methods:
- Investigating transcriptional regulation of HIV-1.
- Identifying small molecules (LRAs) that induce HIV-1 transcription.
- Analyzing studies on combinations of LRAs and their scheduling.
Main Results:
- Understanding HIV-1 transcriptional repression mechanisms.
- Identification of LRAs like histone deacetylase inhibitors and protein kinase C agonists.
- Evidence suggests optimized 'shock and kill' via LRA combinations.
Conclusions:
- Combining LRAs is a promising therapeutic strategy for HIV-1 latency.
- Targeting HIV-1 transcriptional mechanisms is key to eradication.
- Further research into LRA combinations may lead to a functional cure for HIV.
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