Gnidimacrin, a Potent Anti-HIV Diterpene, Can Eliminate Latent HIV-1 Ex Vivo by Activation of Protein Kinase C β.
Journal Article (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 12, 2015
Published In
Volume / Issue
- 58 / 21
Start / End Page
- 8638 - 8646
PubMed ID
- 26509731
Pubmed Central ID
- PMC4767159
Electronic International Standard Serial Number (EISSN)
- 1520-4804
Digital Object Identifier (DOI)
- 10.1021/acs.jmedchem.5b01233
Language
- eng
Conference Location
- United States