Elimination of HIV-1 Latently Infected Cells by Gnidimacrin and a Selective HDAC Inhibitor.
Basic Information
ID: ALA4251706
Journal: ACS Med Chem Lett
Title: Elimination of HIV-1 Latently Infected Cells by Gnidimacrin and a Selective HDAC Inhibitor.
Authors: Huang L, Lai WH, Zhu L, Li W, Wei L, Lee KH, Xie L, Chen CH.
Abstract: 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.
CiteXplore: 29541372
DOI: 10.1021/acsmedchemlett.8b00012
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