The latent HIV reservoir in the brain of people with HIV under antiretroviral therapy (scATAC-Seq). The latent HIV reservoir in the brain of people with HIV under antiretroviral therapy (scATAC-Seq)

A growing body of data suggests that the human brain serves as a sanctuary for HIV persistence despite life-long antiretroviral therapy. Microglia, the innate immune cells of the brain parenchyma, may serve as a reservoir for rebound of HIV infection. The extent of the latent brain reservoir and molecular phenotype of HIV infected microglia cells, however, are unknown. To address this major knowledge gap, we leveraged the ‘Last Gift’ rapid autopsy cohort to perform a multi-omics approach (single cell RNA-seq, single cell ATAC-seq, and H3K27ac ChIP-seq) of the myeloid compartment creating a gene expression and chromatin accessibility atlas of human microglia isolated from three male individuals with HIV on suppressive antiretroviral therapy. Overall design: CD45+ cells were isolated from the frontal cortex (Brodman area 9) of individuals infected with HIV

越来越多的研究证据表明，即便接受终身抗逆转录病毒治疗，人类大脑仍是HIV持续潜伏的庇护所。脑实质的固有免疫细胞——小胶质细胞（microglia），可能是HIV感染反弹的病毒储存库。然而，大脑潜伏病毒储存库的规模以及HIV感染小胶质细胞的分子表型，目前仍不明确。为填补这一重大认知空白，本研究依托「Last Gift」快速尸检队列，对髓系细胞区室开展多组学分析（单细胞RNA测序（single cell RNA-seq）、单细胞ATAC测序（single cell ATAC-seq）以及H3K27ac染色质免疫沉淀测序（H3K27ac ChIP-seq）），构建了来自3名接受抑制性抗逆转录病毒治疗的HIV感染男性个体的人类小胶质细胞的基因表达与染色质可及性图谱。实验整体设计：从HIV感染者的额叶皮层（Brodmann 9区）分离CD45阳性细胞。