School of Pharmaceutical Sciences and Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361005, China.
Medical Center of Hematology, The Second Affiliated Hospital, Army Medical University, Chongqing, China.
Dis Markers. 2022 Feb 7;2022:6055347. doi: 10.1155/2022/6055347. eCollection 2022.
The principal barrier for the eradication of HIV/AIDS is the virus latency. One of the effective strategies so called "shock and kill" is to use latency-reversing agents (LRAs) to activate the latent HIV reservoirs and then combine them with the highly active antiretroviral therapy (HAART) to eradicate the virus. However, most of the current LRAs are too toxic; therefore, they have not been used clinically. Our preliminary data indicated that polyphenols from grape seeds can activate HIV in latently infected Jurkat T cells. Owing to a lot of food containing polyphenols and based on a reasoning whether all of these kinds of polyphenols contain the latency-reversing function, in this study, we screened 22 fruits/vegetables to see whether polyphenols from these can reactivate latent HIV-1 transcription. We finally proved that the polyphenols from grape seeds, apple, pomegranate, and bilberry can reactivate latent HIV-1 transcription. The activation of which can be detected on the level of protein and mRNA. The activation of which is in a dose- and time-dependent manner, while the activated polyphenol extracts have the effects to stimulate Tat-independent HIV-1 transcription. The mechanism shows that polyphenol extracts from grape seeds and apple can stimulate P-TEFb's release from 7SK snRNP to induce HIV gene transcription. These results indicate that using a few food of high-content polyphenols as latent activators and combining HARRT may be of great use for the treatment of HIV/AIDS in the future.
HIV/AIDS 根除的主要障碍是病毒潜伏。所谓的“休克和杀伤”有效策略之一是使用潜伏逆转剂（LRA）来激活潜伏的 HIV 储库，然后将其与高效抗逆转录病毒疗法（HAART）结合使用，以消灭病毒。然而，目前大多数 LRA 毒性太大；因此，它们尚未在临床上使用。我们的初步数据表明，葡萄籽中的多酚可以激活潜伏感染的 Jurkat T 细胞中的 HIV。由于许多含有多酚的食物，并且基于是否所有这些多酚都含有潜伏逆转功能的推理，在这项研究中，我们筛选了 22 种水果/蔬菜，以了解这些多酚是否可以重新激活潜伏的 HIV-1 转录。我们最终证明，葡萄籽、苹果、石榴和越橘中的多酚可以重新激活潜伏的 HIV-1 转录。这种激活可以在蛋白质和 mRNA 水平上检测到。其激活呈剂量和时间依赖性，而激活的多酚提取物具有刺激 Tat 非依赖性 HIV-1 转录的作用。该机制表明，葡萄籽和苹果中的多酚提取物可以刺激 P-TEFb 从 7SK snRNP 中释放出来，从而诱导 HIV 基因转录。这些结果表明，未来使用几种高含量多酚的食物作为潜伏激活剂并结合 HARRT 可能对 HIV/AIDS 的治疗有很大帮助。
