Infectious Disease Division, Brigham and Women's Hospital, Boston, MA, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Nat Rev Microbiol. 2024 Jun;22(6):328-344. doi: 10.1038/s41579-024-01010-8. Epub 2024 Feb 9.
Successful approaches for eradication or cure of HIV-1 infection are likely to include immunological mechanisms, but remarkably little is known about how human immune responses can recognize and interact with the few HIV-1-infected cells that harbour genome-intact viral DNA, persist long term despite antiretroviral therapy and represent the main barrier to a cure. For a long time regarded as being completely shielded from host immune responses due to viral latency, these cells do, on closer examination with single-cell analytic techniques, display discrete footprints of immune selection, implying that human immune responses may be able to effectively engage and target at least some of these cells. The failure to eliminate rebound-competent virally infected cells in the majority of persons likely reflects the evolution of a highly selected pool of reservoir cells that are effectively camouflaged from immune recognition or rely on sophisticated approaches for resisting immune-mediated killing. Understanding the fine-tuned interplay between host immune responses and viral reservoir cells will help to design improved interventions that exploit the immunological vulnerabilities of HIV-1 reservoir cells.
成功根除或治愈 HIV-1 感染的方法可能包括免疫机制，但人们对人类免疫反应如何识别和与少数携带完整基因组病毒 DNA 的 HIV-1 感染细胞相互作用知之甚少，这些细胞尽管接受了抗逆转录病毒治疗，但仍能长期存在，是治愈的主要障碍。这些细胞由于病毒潜伏而长期被认为完全免受宿主免疫反应的影响，但通过单细胞分析技术的更仔细检查，它们确实显示出免疫选择的离散痕迹，这意味着人类免疫反应可能能够有效地参与并针对这些细胞中的至少一些。在大多数人中未能消除具有反弹能力的病毒感染细胞，可能反映了储备细胞的高度选择池的演变，这些细胞有效地逃避了免疫识别，或者依靠复杂的方法来抵抗免疫介导的杀伤。了解宿主免疫反应和病毒储备细胞之间的精细相互作用将有助于设计改进的干预措施，利用 HIV-1 储备细胞的免疫脆弱性。
