Panaampon Jutatip, Kudo Eriko, Kariya Ryusho, Okada Seiji
Division of Hematopoiesis, Graduate School of Medical Sciences, and Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
Heliyon. 2019 Sep 26;5(9):e02490. doi: 10.1016/j.heliyon.2019.e02490. eCollection 2019 Sep.
HIV-1 persists during antiretroviral therapy (ART) due to long-lived and proliferating latently-infected host cells, with the outcome being an incomplete cure. The latently-infected cells, or reservoir cells, are transcriptionally absent and invisible to the immune response. Elimination of latency is one strategy in activating virus production, making it visible to immune clearance. We previously showed that Ephedrae herba reactivated HIV-1 from latency. In this study, we used ephedrine, a major component of Ephedra herba, to reactivate HIV-1 from latency. The results showed that ephedrine enhances HIV-1 reactivation in the presence of TNFα. Combination treatment demonstrates a synergistic effect of HIV-1 reactivation compared to TNFα alone. Ephedrine treatment shows a higher TNFRII expression level, which is related to increased HIV-1 reactivation. However, the mechanism of ephedrine in HIV-1 reactivation is still unclear, and may be related to TNFRII receptor expression. Our results indicate that ephedrine enhances HIV-1 reactivation from latency in combination with TNFα treatment. This new reagent could be a promising latency reversal agent (LRA).
在抗逆转录病毒疗法（ART）期间，HIV-1会因长寿且增殖的潜伏感染宿主细胞而持续存在，其结果是无法实现完全治愈。潜伏感染的细胞，即储存库细胞，转录沉默，免疫反应无法察觉。消除潜伏状态是激活病毒产生从而使其能被免疫清除的一种策略。我们之前表明麻黄可使潜伏的HIV-1重新激活。在本研究中，我们使用麻黄的主要成分麻黄碱来使潜伏的HIV-1重新激活。结果显示，在存在肿瘤坏死因子α（TNFα）的情况下，麻黄碱可增强HIV-1的重新激活。联合治疗与单独使用TNFα相比，对HIV-1重新激活具有协同作用。麻黄碱治疗显示出更高的肿瘤坏死因子受体II（TNFRII）表达水平，这与HIV-1重新激活增加有关。然而，麻黄碱在HIV-1重新激活中的机制仍不清楚，可能与TNFRII受体表达有关。我们的结果表明，麻黄碱与TNFα联合治疗可增强潜伏HIV-1的重新激活。这种新试剂可能是一种有前景的潜伏逆转剂（LRA）。
