Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Infectious Diseases Department, Liège University Hospital, Liège, Belgium.
Laboratory of Viral Immune Pathogenesis, Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Cell Rep. 2020 Feb 18;30(7):2284-2296.e3. doi: 10.1016/j.celrep.2020.01.071.
The HIV latent reservoir forms the major hurdle to an HIV cure. The discovery of CD32 as marker of this reservoir has aroused much interest, but subsequent reports have challenged this finding. Here, we observe a positive correlation between the percentages of CD32 cells among CD4 T cells of aviremic cART-treated, HIV-infected individuals and their HIV DNA loads in peripheral blood. Moreover, optimization of the CD32CD4 T cell purification protocol reveals prominent enrichment for HIV DNA (mean, 292-fold) in these cells. However, no enrichment for HIV RNA is observed in CD32CD4 cells, yielding significantly reduced HIV RNA/DNA ratios. Furthermore, HIV proviruses in CD32CD4 cells can be reactivated ex vivo to produce virus, strongly suggesting that these cells support HIV transcriptional latency. Our results underscore the importance of isolating pure, bona fide CD32CD4 T cells for future studies and indicate that CD32 remains a promising candidate marker of the HIV reservoir.
HIV 潜伏库是 HIV 治愈的主要障碍。CD32 作为该储库标志物的发现引起了广泛关注，但随后的报告对这一发现提出了质疑。在这里，我们观察到，在接受抗病毒治疗、HIV 感染的无病毒血症个体的 CD4 T 细胞中 CD32 细胞的百分比与其外周血中的 HIV DNA 载量之间存在正相关关系。此外，对 CD32+CD4+T 细胞纯化方案的优化显示，这些细胞中 HIV DNA 的富集程度非常显著（平均 292 倍）。然而，在 CD32+CD4 细胞中并未观察到 HIV RNA 的富集，导致 HIV RNA/DNA 比值显著降低。此外，CD32+CD4 细胞中的 HIV 前病毒可以在体外被重新激活以产生病毒，这强烈表明这些细胞支持 HIV 转录潜伏期。我们的研究结果强调了为未来研究分离纯合、真实的 CD32+CD4+T 细胞的重要性，并表明 CD32 仍然是 HIV 储库的一个有前途的候选标志物。
