Department of Tropical Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
Center for Cardiovascular Research, John A.Burns School of Medicine,Honolulu,HI,USA.
Platelets. 2021 Nov 17;32(8):1038-1042. doi: 10.1080/09537104.2020.1849606. Epub 2020 Nov 23.
There are approximately 38 million people globally living with Human immunodeficiency virus 1 (HIV-1) and given the tremendous success of combination antiretroviral therapy (cART) this has dramatically reduced mortality and morbidity with prevention benefits. However, HIV-1 persists during cART within the human body and re-appears upon cART interruption. This HIV-1 reservoir remains a barrier to cure with cellular sites of viral persistence not fully understood. In this study we provide evidence corroborating a recently published article in STM demonstrating the role of platelets as a novel cellular disseminator of HIV-1 particles in the setting of viral suppression. Using classical transmission electron microscopy with and without immunogold labeling, we visualize HIV-1 in both platelets and monocytes in cART suppressed HIV donors. Our study suggests that due to the close proximity of platelets and monocytes an alternative life cycle of HIV-1 cycling within monocytes and platelets without the need of active replication under cART occurs. Our findings are supported by the lack of detectable HIV-1 particles in platelets derived from HIV uninfected donors or the 'Berlin' patient suggesting that platelets may serve as an underappreciated hidden bearer for HIV-1 and should be considered in HIV remission studies and trials.
全球约有 3800 万人感染人类免疫缺陷病毒 1(HIV-1)。由于联合抗逆转录病毒疗法(cART)的巨大成功,死亡率和发病率显著降低,同时也带来了预防效益。然而,HIV-1 在 cART 期间仍在人体内存活,并在 cART 中断后重新出现。这个 HIV-1 储存库仍然是治愈的障碍,细胞内病毒持续存在的部位尚未完全了解。在这项研究中,我们提供了证据支持最近在 STM 上发表的一篇文章,该文章证明了血小板作为 HIV-1 颗粒在病毒抑制环境中的新型细胞传播者的作用。我们使用带和不带免疫金标记的经典透射电子显微镜,在接受 cART 抑制的 HIV 供体中观察到了血小板和单核细胞中的 HIV-1。我们的研究表明,由于血小板和单核细胞非常接近,HIV-1 在单核细胞和血小板中循环的替代生命周期在 cART 下不需要主动复制就会发生。我们的发现得到了以下事实的支持:从未感染 HIV 的供体或“柏林”患者中分离出来的血小板中没有检测到 HIV-1 颗粒,这表明血小板可能是 HIV-1 的一个被低估的隐匿携带者,应该在 HIV 缓解研究和试验中加以考虑。