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Virology. 2014 Dec;471-473:1-12. doi: 10.1016/j.virol.2014.08.016. Epub 2014 Oct 11.

Sulfonation pathway inhibitors block reactivation of latent HIV-1.

Author information

1
Nomis 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.
2
Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
3
Morgridge Institute for Research, Madison, WI, USA; Institute for Molecular Virology, University of Wisconsin, Madison, WI, USA; McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA; Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
4
Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
5
Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
6
Nomis 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. Electronic address: jyoung@salk.edu.

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.

KEYWORDS:

Gene expression; HIV-1; Inhibitor; Latency; Primary CD4+ T cells; Reactivation; Sulfonation

PMID:
25310595
PMCID:
PMC4392775
DOI:
10.1016/j.virol.2014.08.016
[Indexed for MEDLINE]
Free PMC Article

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