Gnidimacrin, a Potent Anti-HIV Diterpene, Can Eliminate Latent HIV-1 Ex Vivo by Activation of Protein Kinase C β.

Published

Journal Article

HIV-1-latency-reversing agents, such as histone deacetylase inhibitors (HDACIs), were ineffective in reducing latent HIV-1 reservoirs ex vivo using CD4 cells from patients as a model. This deficiency poses a challenge to current pharmacological approaches for HIV-1 eradication. The results of this study indicated that gnidimacrin (GM) was able to markedly reduce the latent HIV-1 DNA level and the frequency of latently infected cells in an ex vivo model using patients peripheral blood mononuclear cells. GM induced approximately 10-fold more HIV-1 production than the HDACI SAHA or romidepsin, which may be responsible for the effectiveness of GM in reducing latent HIV-1 levels. GM achieved these effects at low picomolar concentrations by selective activation of protein kinase C βI and βII. Notably, GM was able to reduce the frequency of HIV-1 latently infected cells at concentrations without global T cell activation or stimulating inflammatory cytokine production. GM merits further development as a clinical trial candidate for latent HIV-1 eradication.

Full Text

Duke Authors

Cited Authors

  • Lai, W; Huang, L; Zhu, L; Ferrari, G; Chan, C; Li, W; Lee, K-H; Chen, C-H

Published Date

  • November 3, 2015

Published In

Volume / Issue

  • 58 / 21

Start / End Page

  • 8638 - 8646

PubMed ID

  • 26509731

Pubmed Central ID

  • 26509731

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/acs.jmedchem.5b01233

Language

  • eng