title: A Novel Histone Deacetylase Inhibitor, AR-42, Reactivates HIV-1 from Chronically and Latently Infected CD4+T-cells.
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.
authors: Department of Microbiology, The Ohio State University, Columbus, OH, USA.
authors: Jessica M
authors: JM
authors: Mates
authors: Department of Veterinary Biosciences, Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA.
authors: Suresh
authors: S
authors: de Silva
authors: Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Mark
authors: M
authors: Lustberg
authors: Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Kelsey
authors: K
authors: Van Deusen
authors: Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Robert A
authors: RA
authors: Baiocchi
authors: Department of Veterinary Biosciences, Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA; Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA; Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Li
authors: L
authors: Wu
authors: Department of Microbiology, The Ohio State University, Columbus, OH, USA; Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA; Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA.
authors: Jesse J
authors: JJ
authors: Kwiek
keywords: AR-42; HIV reactivation; HIV-1; histone deacetylase; kick and kill