Latent HIV reservoir is a major barrier to absolute HIV cure. Studies on latency reversal agents (LRA) have by far focused mainly on CD4+ T-lymphocytes, while myeloid reservoirs remain under-represented despite their persistence and key contribution to HIV pathogenesis. cAMP has been shown to increase HIV-1 transcription in latently-infected monocytes/macrophages. In this communication, we explored the potential of commercially available pharmacological drugs and phosphodiesterase inhibitors to reactivate HIV in latently-infected monocytic cell-line, U1. We showed that increased levels of intracellular cAMP reverse HIV latency in vitro, which is specific to cells of the myeloid lineage. High throughput RNA-seq analysis revealed that cAMP modulates transcriptional profile of latently HIV-infected cells and provides favourable cellular environment for HIV to produce viral proteins. This reactivation of latent HIV was inhibited by Mithramycin A, a selective Sp1 inhibitor, indicating that the reversal of HIV latency in monocytes is driven by transcription factor Sp1.

中文翻译：

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转录谱分析表明cAMP驱动的单核细胞HIV潜伏期逆转通过转录因子SP-1发生。

潜在的艾滋病毒储存库是绝对治愈艾滋病毒的主要障碍。潜伏期逆转剂（LRA）的研究到目前为止主要集中在CD4 + T淋巴细胞上，而髓样储集层的持久性和对HIV发病机理的关键贡献仍然不足。已证明，cAMP可在潜伏感染的单核细胞/巨噬细胞中增加HIV-1转录。在本交流中，我们探讨了市售药理药物和磷酸二酯酶抑制剂重新激活潜伏感染的单核细胞系U1中的HIV的潜力。我们显示出增加的细胞内cAMP水平逆转了HIV在体外的潜伏期，这对髓系谱系的细胞是特定的。高通量RNA序列分析表明，cAMP可以调节HIV潜伏感染细胞的转录谱，并为HIV生产病毒蛋白提供有利的细胞环境。潜在的HIV的这种重新激活被选择性Sp1抑制剂Mithramycin A抑制，表明单核细胞中HIV潜伏期的逆转是由转录因子Sp1驱动的。