Journal article
Benzotriazoles Reactivate Latent HIV-1 through Inactivation of STAT5 SUMOylation
Cell reports (Cambridge), Vol.18(5), pp.1324-1334
01/31/2017
DOI: 10.1016/j.celrep.2017.01.022
PMCID: PMC5461578
PMID: 28147284
Abstract
The presence of latent HIV-1 in infected individuals represents a major barrier preventing viral eradication. For that reason, reactivation of latent viruses in the presence of antiretroviral regimens has been proposed as a therapeutic strategy to achieve remission. We screened for small molecules and identified several benzotriazole derivatives with the ability to reactivate latent HIV-1. In the presence of IL-2, benzotriazoles reactivated and reduced the latent reservoir in primary cells, and, remarkably, viral reactivation was achieved without inducing cell proliferation, T cell activation, or cytokine release. Mechanistic studies showed that benzotriazoles block SUMOylation of phosphorylated STAT5, increasing STAT5's activity and occupancy of the HIV-1 LTR. Our results identify benzotriazoles as latency reversing agents and STAT5 signaling and SUMOylation as targets for HIV-1 eradication strategies. These compounds represent a different direction in the search for "shock and kill" therapies.
Details
- Title: Subtitle
- Benzotriazoles Reactivate Latent HIV-1 through Inactivation of STAT5 SUMOylation
- Creators
- Alberto Bosque - University of UtahKyle A. Nilson - University of IowaAmanda B. Macedo - University of UtahAdam M. Spivak - University of UtahNancie M. Archin - University of North Carolina at Chapel HillRyan M. Van Wagoner - University of UtahLaura J. Martins - University of UtahCamille L. Novis - University of UtahMatthew A. Szaniawski - University of UtahChris M. Ireland - University of UtahDavid M. Margolis - University of North Carolina at Chapel HillDavid H. Price - University of IowaVicente Planelles - University of Utah
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.18(5), pp.1324-1334
- Publisher
- Elsevier
- DOI
- 10.1016/j.celrep.2017.01.022
- PMID
- 28147284
- PMCID
- PMC5461578
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Number of pages
- 11
- Grant note
- R01 GM35500 / National Institute of General Medical Sciences of the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 5T32 DK007115-40 / National Institute of Diabetes and Digestive and Kidney Diseases of the NIH under Ruth L. Kirschtein National Research Service R21/R33 AI116212; U19 AI096113 / National Institute of Allergy and Infectious Diseases of the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R21AI116212 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) University of Iowa Presidential Graduate Fellowship T32DK007115 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01GM035500 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 108014-49-RGRL / amfAR research grant
- Language
- English
- Date published
- 01/31/2017
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984288734002771
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