https://ror.org/01vf2g217 Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA, USA
https://ror.org/01vf2g217 Department of Neurosciences, University of California San Diego, San Diego, CA, USA.
Life Sci Alliance. 2024 Jul 26;7(10). doi: 10.26508/lsa.202402736. Print 2024 Oct.
The presence of HIV in sequestered reservoirs is a central impediment to a functional cure, allowing HIV to persist despite life-long antiretroviral therapy (ART), and driving a variety of comorbid conditions. Our understanding of the latent HIV reservoir in the central nervous system is incomplete, because of difficulties in accessing human central nervous system tissues. Microglia contribute to HIV reservoirs, but the molecular phenotype of HIV-infected microglia is poorly understood. We leveraged the unique "Last Gift" rapid autopsy program, in which people with HIV are closely followed until days or even hours before death. Microglial populations were heterogeneous regarding their gene expression profiles but showed similar chromatin accessibility landscapes. Despite ART, we detected occasional microglia containing cell-associated HIV RNA and HIV DNA integrated into open regions of the host's genome (∼0.005%). Microglia with detectable HIV RNA showed an inflammatory phenotype. These results demonstrate a distinct myeloid cell reservoir in the brains of people with HIV despite suppressive ART. Strategies for curing HIV and neurocognitive impairment will need to consider the myeloid compartment to be successful.
HIV 存在于隔离储库中，是实现功能性治愈的主要障碍，这使得 HIV 能够在终身抗逆转录病毒治疗 (ART) 下持续存在，并导致各种合并症。由于难以获取人体中枢神经系统组织，我们对中枢神经系统中潜伏的 HIV 储库的了解还不完整。小胶质细胞有助于 HIV 储库的形成，但 HIV 感染的小胶质细胞的分子表型仍知之甚少。我们利用独特的“最后礼物”快速尸检计划，该计划密切关注 HIV 感染者，直到他们死亡前几天甚至几小时。小胶质细胞群体在基因表达谱上存在异质性，但表现出相似的染色质可及性图谱。尽管进行了 ART，我们仍偶尔检测到含有细胞相关 HIV RNA 和整合到宿主基因组开放区域的 HIV DNA 的小胶质细胞（约 0.005%）。具有可检测到的 HIV RNA 的小胶质细胞表现出炎症表型。这些结果表明，尽管进行了抑制性 ART，HIV 感染者的大脑中仍存在独特的髓样细胞储库。要成功治愈 HIV 和神经认知障碍，就需要考虑髓样细胞。
