HIV病毒库清除策略研究进展

HIV病毒库的长期存在是HIV患者持续感染和难以彻底治愈的重要原因。目前以高效抗反转录病毒疗法为核心的治疗手段还难以将病毒库彻底清除。研究证实HIV病毒库存在于多种类型的CD4~+T细胞内,包括中心记忆CD4~+T细胞、CCR4~+CCR6~+和CXCR3~+CCR6~+CD4~+T细胞、干细胞样记忆CD4~+T细胞、Vγ9Vδ2 T细胞及近期证实的滤泡辅助性T细胞等,而且有研究发现巨噬细胞、B细胞中也可能存在病毒库。当前HIV病毒库清除的策略主要有CCR5基因缺陷造血干细胞移植,基因编辑及激活然后杀死等,但这些方法仍然不能有效清除HIV病毒库。最新研究发现HIV潜伏的CD4~+T细胞表面CD32a分子特异性高表达,这为病毒库的清除带来新的希望。本文旨在综述可能存在HIV病毒库的免疫细胞及HIV病毒库清除策略的研究进展。

Research advance in the strategies for the eradication of HIV reservoir

The persistence of HIV reservoir is an important cause of persistent infection and difficult to cure in HIV patients. It is difficult to completely remove the viral reservoir with HAART at present. Studies have confirmed that HIV reservoir exists in various types of CD4+ T cells, including central memory CD4+ T cells, CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T cells, stem cell like memory CD4+ T cells, Vγ9Vδ2 T cells and recently confirmed Tfh cells. In addition, studies have also found that macrophages and B cells also couple with viral reservoir. Currently, HIV reservoir eradication strategies mainly include CCR5 gene defective hematopoietic stem cell transplantation, gene editing and activation then killing. These methods still can not effectively remove HIV reservoir. Recent studies have shown the specifically high expression of CD32a molecules on the surface of HIV latent CD4+ T cells, which provides new marker for the elimination of viral reservoir. We review the possible immunocytes with HIV reservoir and the research progress on the eradication strategies of HIV reservoir.