Elimination of HIV-1 Latently Infected Cells by Gnidimacrin and a Selective HDAC Inhibitor.

Published online

Journal Article

We have previously reported gnidimacrin (GM), a protein kinase C (PKC) agonist, significantly reduces the frequency of HIV-1 latently infected cells in peripheral blood mononuclear cells (PBMCs) from patients undergoing successful antiretroviral therapy at low picomolar concentrations ex vivo, which is distinct from other latency reversing agents. In this study, we demonstrate that strong viral reactivation by GM is a mechanism for elimination of latently infected cells, and a histone deacetylase inhibitor (HDACI), a thiophenyl benzamide (TPB), further potentiated the efficacy of GM against latent HIV-1. The effect of GM on latent HIV-1 activation was potentiated by TPB in cell models by 2-3-fold. The GM/TPB combination further decreased the frequency of HIV-infected cells in latently infected patient PBMCs over 3-fold when compared with GM alone, which caused a 5-fold reduction compared with the solvent control. Thus, GM/TPB is a unique combination that may reduce latent HIV-1 reservoirs at nontoxic concentrations.

Full Text

Duke Authors

Cited Authors

  • Huang, L; Lai, W-H; Zhu, L; Li, W; Wei, L; Lee, K-H; Xie, L; Chen, C-H

Published Date

  • March 8, 2018

Published In

Volume / Issue

  • 9 / 3

Start / End Page

  • 268 - 273

PubMed ID

  • 29541372

Pubmed Central ID

  • 29541372

International Standard Serial Number (ISSN)

  • 1948-5875

Digital Object Identifier (DOI)

  • 10.1021/acsmedchemlett.8b00012

Language

  • eng

Conference Location

  • United States