Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.
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http://dx.doi.org/10.1016/j.phytochem.2022.113395 | DOI Listing |
J Virol
December 2024
Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
HIV-1 can integrate viral DNA into host cell chromosomes and establish a long-term stable latent viral reservoir, a major obstacle in curing HIV-1 infection. The reactivation of latent proviruses with latency-reversing agents (LRAs) is a prerequisite for the eradication of viral reservoirs. Previous reports have shown that tannic acid (TA) exerts several biological functions, including antioxidant and antitumor activities.
View Article and Find Full Text PDFiScience
December 2024
Department of Biochemistry and Molecular Biology, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
HIV-1 latency is regulated by chromatin modifying enzymes, and histone deacetylase inhibitors (HDACi) cause reactivation of provirus expression. Surprisingly, we observed that inhibitors of the CBP/p300 acetyltransferases also cause reversal of latency in T cells. CBP/p300 inhibitors synergize with various latency reversing agents to cause HIV-1 reactivation.
View Article and Find Full Text PDFCurr HIV/AIDS Rep
November 2024
The Wistar Institute, Philadelphia, PA, USA.
Purpose Of Review: Combination antiretroviral therapy (cART) does not act on latent HIV reservoirs, and no latency-reversing agent (LRA) to date consistently reduces viral reservoirs in humans. In Sub-Saharan Africa and elsewhere, complementary and alternative medicines (CAM) are traditionally used to manage HIV/AIDS, including a subset with LRA properties.
Recent Findings: Several plants from the Euphorbiaceae and Thymelaeaceae families have been recently documented for traditional HIV/AIDS management and contain LRAs that function through protein kinase C activation.
bioRxiv
November 2024
U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Elimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq).
View Article and Find Full Text PDFViruses
November 2024
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
The latent viral reservoir represents one of the major barriers to curing HIV-1. Focus on the "kick and kill" (also called "shock and kill") approach, in which virus expression is reactivated, and then cells producing virus are selectively depleted, has led to the discovery of many latency-reversing agents (LRAs) that have furthered our understanding of the mechanisms driving HIV-1 latency and latency reversal. Thus far, individual compounds have yet to be robust enough to work as a therapy, highlighting the importance of identifying new compounds that target novel pathways and synergize with known LRAs.
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