Anti-HIV Activities and Mechanism of 12-O-Tricosanoylphorbol-20-acetate, a Novel Phorbol Ester from Ostodes katharinae.
Anti-HIV Activities and Mechanism of 12-O-Tricosanoylphorbol-20-acetate, a Novel Phorbol Ester from Ostodes katharinae.
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新型佛波醇酯 12-O-二十三烷酰佛波醇-20-乙酸酯的抗 HIV 活性及机制
DOI：
10.3390/molecules22091498
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Zheng YT
中科院分区：
文献类型：
--
作者：
Chen H;Zhang R;Luo RH;Yang LM;Wang RR;Hao XJ;Zheng YT
APOBEC 3G是人胞苷脱氨酶家族的成员，其通过与子代病毒体包装并在子代病毒感染新细胞时在HIV-1病毒DNA合成期间诱导G至A突变来限制Vif缺陷型病毒。HIV-1 Vif蛋白通过介导A3 G降解来抵抗A3 G的活性。佛波酯是一种植物源性二萜类化合物，属于惕各烷家族，可激活PKC通路。本研究从大戟科（Euphorbiaceae）的狭叶木（Ostodes katharinae）中分离得到一种新的佛波醇酯12-O-二十三烷酰基佛波醇-20-乙酸酯（hop-8），抑制野生型HIV-1和HIV-2病毒株的复制，C8166细胞和PBMCs中的耐药菌株具有较低的细胞毒性，EC 50值范围为0.106 μM至7.987 μM。hop-8的主要机制之一是刺激A3 G在HIV-1产生细胞中的表达并上调子代病毒粒子中的A3 G水平，这导致降低子代病毒的感染性。这种hop-8抑制HIV复制的新机制可能代表了开发HIV感染新疗法的有希望的方法。
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.
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