A Novel Histone Deacetylase Inhibitor, AR-42, Reactivates HIV-1 from Chronically and Latently Infected CD4+ T-cells

Jessica M Mates; Suresh de Silva; Mark Lustberg; Kelsey Van Deusen; Robert A Baiocchi; Li Wu; Jesse J Kwiek

doi:10.4137/RRT.S31632

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A Novel Histone Deacetylase Inhibitor, AR-42, Reactivates HIV-1 from Chronically and Latently Infected CD4+ T-cells

Journal article

Peer reviewed

A Novel Histone Deacetylase Inhibitor, AR-42, Reactivates HIV-1 from Chronically and Latently Infected CD4+ T-cells

Jessica M Mates, Suresh de Silva, Mark Lustberg, Kelsey Van Deusen, Robert A Baiocchi, Li Wu and Jesse J Kwiek

Retrovirology : Research and Treatment, Vol.7(2015), pp.1-5

2015

DOI: 10.4137/RRT.S31632

PMCID: PMC4739806

PMID: 26855567

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Abstract

Human immunodeficiency virus type 1 (HIV-1) latency is a major barrier to a cure of AIDS. Latently infected cells harbor an integrated HIV-1 genome but are not actively producing HIV-1. Histone deacetylase (HDAC) inhibitors, such as vorinostat (SAHA), have been shown to reactivate latent HIV-1. AR-42, a modified HDAC inhibitor, has demonstrated efficacy against malignant melanoma, meningioma, and acute myeloid leukemia and is currently used in clinical trials for non-Hodgkin’s lymphoma and multiple myeloma. In this study, we evaluated the ability of AR-42 to reactivate HIV-1 in the two established CD4 + T-cell line models of HIV-1 latency. In HIV-1 chronically infected ACH-2 cells, AR-42-induced histone acetylation was more potent and robust than that of vorinostat. Although AR-42 and vorinostat were equipotent in their ability to reactivate HIV-1, AR-42-induced maximal HIV-1 reactivation was twofold greater than vorinostat in ACH-2 and J-Lat (clone 9.2) cells. These data provide rationale for assessing the efficacy of AR-42-mediated HIV-1 reactivation within primary CD4 + T-cells.

HIV-1

kick and kill

AR-42

histone deacetylase

HIV reactivation

Details

Title: Subtitle: A Novel Histone Deacetylase Inhibitor, AR-42, Reactivates HIV-1 from Chronically and Latently Infected CD4+ T-cells
Creators: Jessica M Mates - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Suresh de Silva - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Mark Lustberg - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Kelsey Van Deusen - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Robert A Baiocchi - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Li Wu - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Jesse J Kwiek - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Resource Type: Journal article
Publication Details: Retrovirology : Research and Treatment, Vol.7(2015), pp.1-5
DOI: 10.4137/RRT.S31632
PMID: 26855567
PMCID: PMC4739806
NLM abbreviation: Retrovirology (Auckl)
ISSN: 1178-1238
eISSN: 1178-1238
Language: English
Date published: 2015
Academic Unit: Microbiology and Immunology
Record Identifier: 9984002386202771

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