Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Department of Basic Science, Faculty of Science and Technology, Kampala International University-Western Campus, P.O. Box 71, Bushenyi, Uganda.
Viruses. 2020 Sep 18;12(9):1040. doi: 10.3390/v12091040.
The C-promoter binding factor-1 (CBF-1) is a potent and specific inhibitor of the human immunodeficiency virus (HIV)-1 LTR promoter. Here, we demonstrate that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. Chromatin immunoprecipitation (ChIP) assays using latently infected primary T cells and Jurkat T-cell lines demonstrated that CBF-1 induces the establishment and maintenance of HIV latency by recruiting polycomb group (PcG/PRC) corepressor complexes or polycomb repressive complexes 1 and 2 (PRC1 and PRC2). Knockdown of CBF-1 resulted in the dissociation of PRCs corepressor complexes enhancing the recruitment of RNA polymerase II (RNAP II) at HIV LTR. Knockdown of certain components of PRC1 and PRC2 also led to the reactivation of latent proviruses. Similarly, the treatment of latently infected primary CD4+ T cells with the PRC2/EZH2 inhibitor, 3-deazaneplanocin A (DZNep), led to their reactivation.
C 启动子结合因子-1（CBF-1）是一种有效的、特异性的人类免疫缺陷病毒（HIV）-1 LTR 启动子抑制剂。在这里，我们证明，使用特异性短发夹 RNA（shRNA）敲低潜伏感染的原代 CD4+ T 细胞中的内源性 CBF-1，会导致潜伏 HIV 前病毒的重新激活。使用潜伏感染的原代 T 细胞和 Jurkat T 细胞系进行的染色质免疫沉淀（ChIP）分析表明，CBF-1 通过募集多梳体（PcG/PRC）核心抑制复合物或多梳抑制复合物 1 和 2（PRC1 和 PRC2），诱导 HIV 潜伏期的建立和维持。CBF-1 的敲低导致 PRC 核心抑制复合物的解离，增强了 HIV LTR 处 RNA 聚合酶 II（RNAP II）的募集。PRC1 和 PRC2 的某些成分的敲低也导致潜伏前病毒的重新激活。同样，用 PRC2/EZH2 抑制剂 3-去氮杂胞苷 A（DZNep）处理潜伏感染的原代 CD4+ T 细胞，也导致它们的重新激活。
