U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
Cells. 2019 Aug 15;8(8):902. doi: 10.3390/cells8080902.
HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in and using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed.
在急性 HIV-1 感染（AHI）期间，HIV-1 会扩散到广泛的组织隔室。中枢神经系统（CNS）可以作为病毒复制的早期和持续部位，这对针对 HIV 储库的 HIV-1 缓解策略构成了潜在挑战。CNS 隔室化是 HIV-1 神经发病机制的一个关键特征。迄今为止，尚不清楚感染后中枢神经系统隔室化发展的时间。我们使用包膜基因的单基因组测序检查了在 AHI 期间 HIV-1 传播/创始（T/F）病毒是否在 CNS 和血液之间存在差异，并使用来自 18 个人的配对血浆和脑脊液（CSF）进一步检查了 和 中的亚区进行了下一代测序。在八个多重 T/F 感染个体中的六个中发现了大多数次要变体的不同比例，这表明 CSF 中某些变体的富集可能导致在感染后期出现明显的隔室化。这项研究首次提供了证据，表明在多重 T/F 感染中，HIV-1 在中枢神经系统中的隔室化可以在 HIV-1 暴露后的几天内发生。需要进一步了解决定 T/F 变体在 CNS 中富集的因素，以及这些发现对 HIV-1 储库持久性和 HIV 神经损伤的潜在长期影响。
