Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Microbiol. 2023 Feb;8(2):260-271. doi: 10.1038/s41564-022-01306-6. Epub 2023 Jan 30.
HIV-1 persists as a latent reservoir in people receiving suppressive antiretroviral therapy (ART). When ART is interrupted (treatment interruption/TI), rebound virus re-initiates systemic infection in the lymphoid system. During TI, HIV-1 is also detected in cerebrospinal fluid (CSF), although the source of this rebound virus is unknown. To investigate whether there is a distinct HIV-1 reservoir in the central nervous system (CNS), we compared rebound virus after TI in the blood and CSF of 11 participants. Peak rebound CSF viral loads vary and we show that high viral loads and the appearance of clonally amplified viral lineages in the CSF are correlated with the transient influx of white blood cells. We found no evidence of rebound macrophage-tropic virus in the CSF, even in one individual who had macrophage-tropic HIV-1 in the CSF pre-therapy. We propose a model in which R5 T cell-tropic virus is released from infected T cells that enter the CNS from the blood (or are resident in the CNS during therapy), with clonal amplification of infected T cells and virus replication occurring in the CNS during TI.
HIV-1 在接受抑制性抗逆转录病毒治疗（ART）的人群中作为潜伏储库持续存在。当 ART 被中断（治疗中断/TI）时，反弹病毒会重新在淋巴系统中引发全身感染。在 TI 期间，虽然反弹病毒的来源未知，但也可以在脑脊液（CSF）中检测到 HIV-1。为了研究中枢神经系统（CNS）中是否存在独特的 HIV-1 储库，我们比较了 11 名参与者血液和 CSF 中的 TI 后反弹病毒。峰值反弹 CSF 病毒载量存在差异，我们表明，高病毒载量和 CSF 中克隆扩增病毒谱系的出现与白细胞的短暂涌入有关。我们没有发现 CSF 中存在反弹巨噬细胞嗜性病毒的证据，即使在一个个体中，该个体在治疗前的 CSF 中就已经存在巨噬细胞嗜性 HIV-1。我们提出了一个模型，其中 R5 T 细胞嗜性病毒是从血液中进入 CNS 的受感染 T 细胞（或在治疗期间驻留在 CNS 中）释放的，在 TI 期间，受感染的 T 细胞和病毒复制在 CNS 中发生克隆扩增。
