Virology 2014-12-01

Sulfonation pathway inhibitors block reactivation of latent HIV-1.

Jeffrey P Murry, Joseph Godoy, Amey Mukim, Justine Swann, James W Bruce, Paul Ahlquist, Alberto Bosque, Vicente Planelles, Celsa A Spina, John A T Young

Index: Virology 471-473 , 1-12, (2014)

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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. Copyright © 2014. Published by Elsevier Inc.