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Updated: Apr 22, 2026
High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Sulfonation pathway inhibitors block reactivation of latent HIV-1
Jeffrey P Murry1, Joseph Godoy2, Amey Mukim2
1Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA; Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Abstract:
Long-lived pools of latently infected cells are a significant barrier to the development of a cure for HIV-1 infection. A better understanding of the mechanisms of reactivation from latency is needed to facilitate the development of novel therapies that address this problem. Here we show that chemical inhibitors of the sulfonation pathway prevent virus reactivation, both in latently infected J-Lat and U1 cell lines and in a primary human CD4+ T cell model of latency. In each of these models, sulfonation inhibitors decreased transcription initiation from the HIV-1 promoter. These inhibitors block transcription initiation at a step that lies downstream of nucleosome remodeling and affects RNA polymerase II recruitment to the viral promoter. These results suggest that the sulfonation pathway acts by a novel mechanism to regulate efficient virus transcription initiation during reactivation from latency, and further that augmentation of this pathway could be therapeutically useful.
Insights
Chemical inhibitors targeting the sulfonation pathway block HIV-1 reactivation from latency. This novel approach inhibits viral transcription initiation, offering a potential therapeutic strategy for HIV-1 cure.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Latent reservoirs of HIV-1-infected cells are a major obstacle to achieving a cure.
- Understanding HIV-1 reactivation mechanisms is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of the sulfonation pathway in HIV-1 reactivation from latency.
- To identify novel therapeutic targets for HIV-1 cure.
Main Methods:
- Utilized J-Lat and U1 cell lines, and primary human CD4+ T cells to model HIV-1 latency.
- Administered chemical inhibitors of the sulfonation pathway to assess their impact on viral reactivation.
- Analyzed transcription initiation from the HIV-1 promoter and RNA polymerase II recruitment.
Main Results:
- Sulfonation pathway inhibitors effectively prevented HIV-1 reactivation in all tested models.
- Inhibitors reduced transcription initiation from the HIV-1 promoter.
- The mechanism involves blocking transcription initiation downstream of nucleosome remodeling, affecting RNA polymerase II recruitment.
Conclusions:
- The sulfonation pathway plays a novel role in regulating HIV-1 transcription initiation during reactivation.
- Augmenting the sulfonation pathway presents a promising therapeutic strategy for HIV-1 cure.
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