BACKGROUND The latent human immunodeficiency virus type 1 (HIV-1) reservoir represents a major barrier to a cure. Based on the levels of HIV-1 DNA in naive (TN) vs resting memory CD4+ T cells, it is widely hypothesized that this reservoir resides primarily within memory cells. Here, we compared virus production from TN and central memory (TCM) CD4+ T cells isolated from HIV-1-infected individuals on suppressive therapy. METHODS CD4+ TN and TCM cells were purified from the blood of 7 HIV-1-infected individuals. We quantified total HIV-1 DNA in the CD4+ TN and TCM cells. Extracellular virion-associated HIV-1 RNA or viral outgrowth assays were used to assess latency reversal following treatment with anti-CD3/CD28 monoclonal antibodies (mAbs), phytohaemagglutinin/interleukin-2, phorbol 12-myristate 13-acetate/ionomycin, prostratin, panobinostat, or romidepsin. RESULTS HIV-1 DNA was significantly higher in TCM compared to TN cells (2179 vs 684 copies/106 cells, respectively). Following exposure to anti-CD3/CD28 mAbs, virion-associated HIV-1 RNA levels were similar between TCM and TN cells (15 135 vs 18 290 copies/mL, respectively). In 4/7 donors, virus production was higher for TN cells independent of the latency reversing agent used. Replication-competent virus was recovered from both TN and TCM cells. CONCLUSIONS Although the frequency of HIV-1 infection is lower in TN compared to TCM cells, as much virus is produced from the TN population after latency reversal. This finding suggests that quantifying HIV-1 DNA alone may not predict the size of the inducible latent reservoir and that TN cells may be an important reservoir of latent HIV-1.

中文翻译：

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幼稚的CD4 + T细胞带有一个可诱导潜伏的，具有复制能力的人免疫缺陷病毒1型病毒的大型诱导库。

背景技术潜在的1型人类免疫缺陷病毒（HIV-1）储库代表了治愈的主要障碍。根据幼稚（TN）与静息记忆CD4 + T细胞中HIV-1 DNA的水平，广泛假设该储存库主要位于记忆细胞内。在这里，我们比较了在抑制疗法中从TN和从HIV-1感染者中分离出的中央记忆（TCM）CD4 + T细胞产生的病毒。方法从7名HIV-1感染者的血液中纯化CD4 + TN和TCM细胞。我们量化了CD4 + TN和TCM细胞中的总HIV-1 DNA。使用抗CD3 / CD28单克隆抗体（mAb），植物血凝素/白介素-2，佛波12-肉豆蔻酸酯13-乙酸酯/离子霉素，前体质素， panobinostat，或罗米地辛。结果与TN细胞相比，TCM中HIV-1 DNA明显更高（分别为2179 vs 684个拷贝/ 106个细胞）。暴露于抗CD3 / CD28 mAb后，中药和TN细胞之间与病毒体相关的HIV-1 RNA水平相似（分别为15 135 vs 18 290拷贝/ mL）。在4/7供体中，独立于所用的潜伏期逆转剂，TN细胞的病毒产量更高。可从TN和TCM细胞中回收具有复制能力的病毒。结论尽管与中药相比，TN中HIV-1感染的频率较低，但潜伏期逆转后，TN人群产生了许多病毒。这一发现表明，仅对HIV-1 DNA进行定量可能无法预测诱导型潜伏库的大小，而TN细胞可能是潜在的HIV-1的重要库。结果与TN细胞相比，TCM中HIV-1 DNA明显更高（分别为2179 vs 684个拷贝/ 106个细胞）。暴露于抗CD3 / CD28 mAb后，中药和TN细胞之间与病毒体相关的HIV-1 RNA水平相似（分别为15 135 vs 18 290拷贝/ mL）。在4/7供体中，独立于所用的潜伏期逆转剂，TN细胞的病毒产量更高。可从TN和TCM细胞中回收具有复制能力的病毒。结论尽管与中药相比，TN中HIV-1感染的频率较低，但潜伏期逆转后，TN人群产生了许多病毒。这一发现表明，仅对HIV-1 DNA进行定量可能无法预测诱导型潜伏库的大小，而TN细胞可能是潜在的HIV-1的重要库。结果与TN细胞相比，TCM中HIV-1 DNA明显更高（分别为2179 vs 684个拷贝/ 106个细胞）。暴露于抗CD3 / CD28 mAb后，中药和TN细胞之间与病毒体相关的HIV-1 RNA水平相似（分别为15 135 vs 18 290拷贝/ mL）。在4/7供体中，独立于所用的潜伏期逆转剂，TN细胞的病毒产量更高。可从TN和TCM细胞中回收具有复制能力的病毒。结论尽管与中药相比，TN中HIV-1感染的频率较低，但潜伏期逆转后，TN人群产生了许多病毒。这一发现表明，仅对HIV-1 DNA进行定量可能无法预测诱导型潜伏库的大小，而TN细胞可能是潜在的HIV-1的重要库。