一场无法治愈的磨难：了解治愈 HIV-1 感染的障碍。
An ordeal that does not heal: understanding barriers to a cure for HIV-1 infection.
机构信息
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
出版信息
Trends Immunol. 2022 Aug;43(8):608-616. doi: 10.1016/j.it.2022.06.002.
With more than 38 million people living with HIV-1 (PLWH) worldwide, developing a cure for HIV-1 remains a major global health priority. Lifelong persistence of HIV-1 is frequently attributed to a pool of stable, transcriptionally silent HIV-1 proviruses, which are unaffected by currently available antiretroviral therapy (ART) or host immune activity. In this opinion article, we propose a more dynamic interpretation of HIV-1 reservoir cell biology and argue that HIV-1 proviruses frequently display residual viral transcriptional activity, making them vulnerable to longitudinal immune-mediated selection processes. Such mechanisms may, over extended periods of ART, induce an attenuated viral reservoir profile characterized by intact proviruses preferentially integrated into heterochromatin locations. We suggest that intensifying and accelerating naturally occurring selection mechanisms might represent a promising strategy for finding a potential cure for HIV-1 infection.
全球有超过 3800 万人感染 HIV-1（PLWH），因此开发治愈 HIV-1 的方法仍然是全球卫生的主要重点。HIV-1 的终身持续存在通常归因于稳定的、转录沉默的 HIV-1 前病毒池，目前可用的抗逆转录病毒疗法（ART）或宿主免疫活性对其没有影响。在这篇观点文章中，我们提出了一种更具动态性的 HIV-1 储存细胞生物学解释，并认为 HIV-1 前病毒经常显示出残留的病毒转录活性，使它们容易受到纵向免疫介导的选择过程的影响。在 ART 的延长时间内，这种机制可能会诱导一种减弱的病毒储存库特征，表现为优先整合到异染色质位置的完整前病毒。我们认为，加强和加速自然发生的选择机制可能是寻找 HIV-1 感染潜在治愈方法的一种有前途的策略。
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