Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain.
Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain.
复制标题
人类大脑中HIV-1储库的鉴定、定量和表征。
作者：
治愈艾滋病毒感染的主要障碍是血液和组织中艾滋病毒宿主的早期生成和延长存活期。目前，用于检测和量化艾滋病毒储存库的技术大多基于基于血液的化验；然而，很明显，病毒储存库仍然留在组织中。我们的研究描述了一种新的多组分成像方法(HIV DNA、mRNA和病毒蛋白在同一检测中)，以识别、量化和表征从HIV感染者获得的组织和血液产品中的病毒库，即使在系统复制无法检测到的情况下也是如此。在接受抗逆转录病毒治疗的HIV感染者的人脑中，我们发现小胶质细胞/巨噬细胞和少量星形胶质细胞是整合了HIV DNA的主要细胞。在整合了HIV DNA的细胞中，只有一半的细胞表达病毒mRNA，三分之一的细胞表达病毒蛋白。令人惊讶的是，我们在HIV感染细胞周围的未感染细胞中发现了残留的HIV-p24、gp120、nef、vpr和Tat蛋白的表达和积累，这表明局部合成、分泌和旁观者摄取。总而言之，我们的数据显示，ART减少了大脑中艾滋病毒储存库的大小；然而，局部/慢性病毒蛋白分泌仍然存在，这表明大脑仍然是治愈艾滋病毒感染的主要解剖目标。
The major barrier to cure HIV infection is the early generation and extended survival of HIV reservoirs in the circulation and tissues. Currently, the techniques used to detect and quantify HIV reservoirs are mostly based on blood-based assays; however, it has become evident that viral reservoirs remain in tissues. Our study describes a novel multi-component imaging method (HIV DNA, mRNA, and viral proteins in the same assay) to identify, quantify, and characterize viral reservoirs in tissues and blood products obtained from HIV-infected individuals even when systemic replication is undetectable. In the human brains of HIV-infected individuals under ART, we identified that microglia/macrophages and a small population of astrocytes are the main cells with integrated HIV DNA. Only half of the cells with integrated HIV DNA expressed viral mRNA, and one-third expressed viral proteins. Surprisingly, we identified residual HIV-p24, gp120, nef, vpr, and tat protein expression and accumulation in uninfected cells around HIV-infected cells suggesting local synthesis, secretion, and bystander uptake. In conclusion, our data show that ART reduces the size of the brain’s HIV reservoirs; however, local/chronic viral protein secretion still occurs, indicating that the brain is still a major anatomical target to cure HIV infection.
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