Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Howard Hughes Medical Institute, Baltimore, MD, USA.
Nat Rev Immunol. 2022 Aug;22(8):499-512. doi: 10.1038/s41577-021-00649-1. Epub 2021 Nov 25.
Combination antiretroviral therapy (ART) can block multiple stages of the HIV-1 life cycle to prevent progression to AIDS in people living with HIV-1. However, owing to the persistence of a reservoir of latently infected CD4 T cells, life-long ART is necessary to prevent viral rebound. One strategy currently under consideration for curing HIV-1 infection is known as 'shock and kill'. This strategy uses latency-reversing agents to induce expression of HIV-1 genes, allowing for infected cells to be cleared by cytolytic immune cells. The role of innate immunity in HIV-1 pathogenesis is best understood in the context of acute infection. Here, we suggest that innate immunity can also be used to improve the efficacy of HIV-1 cure strategies, with a particular focus on dendritic cells (DCs) and natural killer cells. We discuss novel latency-reversing agents targeting DCs as well as DC-based strategies to enhance the clearance of infected cells by CD8 T cells and strategies to improve the killing activity of natural killer cells.
联合抗逆转录病毒疗法（ART）可以阻断 HIV-1 生命周期的多个阶段，从而防止 HIV-1 感染者发展为艾滋病。然而，由于潜伏感染的 CD4 T 细胞库的存在，需要终身进行 ART 以防止病毒反弹。目前正在考虑的一种治愈 HIV-1 感染的策略称为“冲击和杀伤”。该策略使用潜伏逆转剂诱导 HIV-1 基因的表达，使受感染的细胞被细胞毒性免疫细胞清除。先天免疫在 HIV-1 发病机制中的作用在急性感染的背景下得到了最好的理解。在这里，我们建议先天免疫也可以用于提高 HIV-1 治愈策略的疗效，特别关注树突状细胞（DC）和自然杀伤细胞。我们讨论了针对 DC 的新型潜伏逆转剂以及基于 DC 的策略，以增强 CD8 T 细胞清除感染细胞的能力，并改善自然杀伤细胞的杀伤活性。
