Bocklandt Sven, Blumberg Peter M, Hamer Dean H
National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Antiviral Res. 2003 Jul;59(2):89-98. doi: 10.1016/s0166-3542(03)00034-2.
Agents that induce HIV-1 out of latency would be useful adjuvants for currently available anti-retroviral therapy. We report that nanomolar concentrations of 12-deoxyphorbol 13-phenylacetate (DPP), an anti-tumor-promoting phorbol ester originally isolated from a West African plant, induce the expression of HIV-1 in latently infected T cells and render them sensitive to killing by an immunotoxin targeted to the viral envelope glycoprotein. DPP also regulates an extensive series of genes under the control of protein kinase C, including several involved in T cell activation and cytoskeleton reorganization, and represses expression of the HIV-1 receptor CD4 and coreceptor CXCR4. DPP is 20-40-fold more potent than the related phorbol ester prostratin, probably due to its more lipophilic side chain structure. The combination of high potency and anti-tumor promoting activity make DPP an attractive candidate for the adjunctive therapy of persistent HIV-1 infection.
能够使潜伏的HIV-1激活的药物，对于目前可用的抗逆转录病毒疗法而言，将是有用的佐剂。我们报告称，纳摩尔浓度的12-脱氧佛波醇13-苯乙酸酯（DPP），一种最初从一种西非植物中分离出来的具有抗肿瘤促进作用的佛波酯，可诱导潜伏感染的T细胞中HIV-1的表达，并使它们对靶向病毒包膜糖蛋白的免疫毒素杀伤敏感。DPP还调控一系列受蛋白激酶C控制的基因，包括几个参与T细胞活化和细胞骨架重组的基因，并抑制HIV-1受体CD4和共受体CXCR4的表达。DPP的效力比相关佛波酯原卟啉素高20至40倍，这可能是由于其更具亲脂性的侧链结构。高效力和抗肿瘤促进活性的结合，使DPP成为持续性HIV-1感染辅助治疗的有吸引力的候选药物。
