In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin. In the absence of uTat, uDNA minichromatin is gradually silenced, but remains highly inducible by HDAC inhibitors (HDACi). Therefore, functionally, uTat antagonizes uDNA minichromatin repression to maintain persistent viral transcription in macrophages. uTat-mediated viral persistence may establish a viral reservoir in macrophages where uDNA were found to persist.

中文翻译：

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Tat控制人类原代巨噬细胞中未整合的HIV基因组的转录持久性。

在感染了HIV的巨噬细胞中，大量病毒基因组以转录活性的非整合形式（uDNA）的形式持续存在。但是，如何控制这种转录活性仍不清楚。在本报告中，我们研究了转录的病毒反式激活子Tat是否参与uDNA转录。我们证明了从uDNA产生了从头开始的Tat活性，并且此uDNA衍生的Tat（uTat）激活了uDNA LTR。另外，uTat对于组装成抑制性游离型微型染色质的uDNA的转录持久性是必需的。在没有uTat的情况下，uDNA minichromatin逐渐沉默，但仍可被HDAC抑制剂（HDACi）高度诱导。因此，在功能上，uTat拮抗uDNA minichromatin抑制，以维持巨噬细胞中的持续病毒转录。