Background A reservoir of replication-competent but latent virus is the main obstacle to a cure for HIV-1 infection. Much of this reservoir resides in memory CD4 T cells. We hypothesized that these cells can be reactivated with antigens from HIV-1 and other common pathogens to reverse latency. Results We obtained mononuclear cells from the peripheral blood of antiretroviral-treated patients with suppressed viremia. We tested pools of peptides and proteins derived from HIV-1 and from other pathogens including CMV for their ability to reverse latency ex vivo by activation of memory responses. We assessed activation of the CD4 T cells by measuring the up-regulation of cell-surface CD69. We assessed HIV-1 expression using two assays: a real-time PCR assay for virion-associated viral RNA and a droplet digital PCR assay for cell-associated, multiply spliced viral mRNA. Reversal of latency occurred in a minority of cells from some participants, but no single antigen induced HIV-1 expression ex vivo consistently. When reversal of latency was induced by a specific peptide pool or protein, the extent was proportionally greater than that of T cell activation. Conclusions In this group of patients in whom antiretroviral therapy was started during chronic infection, the latent reservoir does not appear to consistently reside in CD4 T cells of a predominant antigen-specificity. Peptide-antigens reversed HIV-1 latency ex vivo with modest and variable activity. When latency was reversed by specific peptides or proteins, it was proportionally greater than the extent of T cell activation, suggesting partial enrichment of the latent reservoir in cells of specific antigen-reactivity.

中文翻译：

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HIV-1、CMV 和其他感染因子抗原对 HIV-1 潜伏期的离体逆转不一致

背景 具有复制能力但潜伏的病毒库是治愈 HIV-1 感染的主要障碍。该储存库大部分位于记忆 CD4 T 细胞中。我们假设这些细胞可以被 HIV-1 和其他常见病原体的抗原重新激活以逆转潜伏期。结果我们从接受抗逆转录病毒治疗且病毒血症受到抑制的患者的外周血中获得了单核细胞。我们测试了源自 HIV-1 和其他病原体（包括 CMV）的肽和蛋白质池，了解它们通过激活记忆反应来逆转离体潜伏期的能力。我们通过测量细胞表面 CD69 的上调来评估 CD4 T 细胞的激活。我们使用两种测定法评估了 HIV-1 的表达：针对病毒颗粒相关病毒 RNA 的实时 PCR 测定法和针对细胞相关多重剪接病毒 mRNA 的液滴数字 PCR 测定法。一些参与者的少数细胞中发生了潜伏期的逆转，但没有单一抗原一致地诱导 HIV-1 离体表达。当特定肽库或蛋白质诱导潜伏期逆转时，其程度比 T 细胞激活的程度更大。结论 在这组在慢性感染期间开始抗逆转录病毒治疗的患者中，潜伏病毒库似乎并不始终驻留在具有主要抗原特异性的 CD4 T 细胞中。肽抗原可在体外逆转 HIV-1 潜伏期，且具有适度且可变的活性。当特定肽或蛋白质逆转潜伏期时，潜伏期的比例大于 T 细胞激活的程度，表明具有特定抗原反应性的细胞中潜伏库部分富集。