Journal Article

Anti-HIV Activities and Mechanism of 12-O-Tricosanoylphorbol-20-acetate, a Novel Phorbol Ester from Ostodes katharinae

Luo, Rong-Hua, Hao, Xiao-Jiang, Chen, Huan, Zhang, Rong, Wang, Rui-Rui, Zheng, Yong-Tang, Yang, Liu-Meng

2017

Overview

APOBEC3G is a member of the human cytidine deaminase family that restricts Vif-deficient viruses by being packaged with progeny virions and inducing the G to A mutation during the synthesis of HIV-1 viral DNA when the progeny virus infects new cells. HIV-1 Vif protein resists the activity of A3G by mediating A3G degradation. Phorbol esters are plant-derived organic compounds belonging to the tigliane family of diterpenes and could activate the PKC pathway. In this study, we identified an inhibitor 12-O-tricosanoylphorbol-20-acetate (hop-8), a novel ester of phorbol which was isolated from Ostodes katharinae of the family Euphorbiaceae, that inhibited the replication of wild-type HIV-1 and HIV-2 strains and drug-resistant strains broadly both in C8166 cells and PBMCs with low cytotoxicity and the EC50 values ranged from 0.106 μM to 7.987 μM. One of the main mechanisms of hop-8 is to stimulate A3G expressing in HIV-1 producing cells and upregulate the A3G level in progeny virions, which results in reducing the infectivity of the progeny virus. This novel mechanism of hop-8 inhibition of HIV replication might represents a promising approach for developing new therapeutics for HIV infection.

• Publisher: MDPI AG,MDPI
• Subject: 12-O-tricosanoylphorbol-20-acetate / Anti-HIV Agents - chemistry / Anti-HIV Agents - isolation & purification / Anti-HIV Agents - pharmacology / antiviral agent / APOBEC-3G Deaminase - genetics / APOBEC-3G Deaminase - metabolism / APOBEC3G / Cell Line / DNA, Viral - antagonists & inhibitors / DNA, Viral - biosynthesis / Drug resistance / Euphorbiaceae - chemistry / Gene Expression Regulation / HIV / HIV-1 - drug effects / HIV-1 - genetics / HIV-1 - metabolism / HIV-2 - drug effects / HIV-2 - genetics / HIV-2 - metabolism / Host-Pathogen Interactions / Human immunodeficiency virus / Humans / Leukocytes, Mononuclear - drug effects / Leukocytes, Mononuclear - metabolism / Leukocytes, Mononuclear - virology / Mutation / phorbol ester / Phorbol Esters - chemistry / Phorbol Esters - isolation & purification / Phorbol Esters - pharmacology / Plant Extracts - chemistry / Primary Cell Culture / Protein Kinase C - genetics / Protein Kinase C - metabolism / Signal Transduction / T-Lymphocytes - drug effects / T-Lymphocytes - metabolism / T-Lymphocytes - virology / Vif / vif Gene Products, Human Immunodeficiency Virus - deficiency / vif Gene Products, Human Immunodeficiency Virus - genetics / Virion - drug effects / Virion - genetics / Virion - metabolism / Virus Replication - drug effects