CBF-1 Promotes the Establishment and Maintenance of HIV Latency by Recruiting Polycomb Repressive Complexes, PRC1 and PRC2, at HIV LTR.
CBF-1 Promotes the Establishment and Maintenance of HIV Latency by Recruiting Polycomb Repressive Complexes, PRC1 and PRC2, at HIV LTR.
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DOI：
10.3390/v12091040
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发表时间：
2020-09-18
期刊：
影响因子：
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通讯作者：
Tyagi M
中科院分区：
文献类型：
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作者：
Sharma AL;Hokello J;Sonti S;Zicari S;Sun L;Alqatawni A;Bukrinsky M;Simon G;Chauhan A;Daniel R;Tyagi M
c -启动子结合因子-1 （CBF-1）是人类免疫缺陷病毒(HIV)-1 LTR启动子的有效特异性抑制剂。在这里，我们证明了在潜伏感染的原发CD4+ T细胞中，使用特异性小发夹rna （shRNA）敲低内源性CBF-1，导致潜伏HIV前病毒的再激活。利用潜伏感染的原代T细胞和Jurkat T细胞系进行的染色质免疫沉淀（ChIP）试验表明，CBF-1通过募集多梳组（PcG/PRC）共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。敲低CBF-1导致PRCs协同抑制复合物的解离，增强了HIV LTR处RNA聚合酶II （RNAP II）的募集，敲低PRC1和PRC2的某些成分也导致潜伏前病毒的再激活。同样，用PRC2/EZH2抑制剂3-deazaneplanocin A （DZNep）治疗潜伏感染的原代CD4+ T细胞可导致其再激活。
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.