RbAp48, a novel inhibitory factor that regulates the transcription of human immunodeficiency virus type 1.
RbAp48, a novel inhibitory factor that regulates the transcription of human immunodeficiency virus type 1.
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DOI：
10.3892/ijmm.2016.2598
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发表时间：
2016-07
影响因子：
5.4
通讯作者：
Juan Wang;Jin Yang;Zongxing Yang;Xiangyun Lu;C. Jin;Lin-fang Cheng;N. Wu
中科院分区：
文献类型：
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作者：
Juan Wang;Jin Yang;Zongxing Yang;Xiangyun Lu;C. Jin;Lin-fang Cheng;N. Wu
视网膜母细胞瘤结合蛋白4（RbAp 48）是一种组蛋白伴侣，已被认为在基因沉默中发挥作用。然而，据我们所知，RbAp 48在人类免疫缺陷病毒1型（HIV-1）感染和基因复制中的作用迄今尚未确定。为此，我们在本研究中证明，RbAp 48的表达上调HIV-1感染，而RbAp 48的敲低促进HIV感染和病毒颗粒的产生。RbAp 48的异位表达抑制HIV-1的表达，这种抑制与HIV-1基因组RNA和各种RNA转录物的表达显著降低相关。进一步确定RbAp 48抑制作用机制的实验表明，RbAp 48的异位表达抑制了HIV-1长末端重复序列（LTR）介导的基础转录以及TNF-α和佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）激活的转录。此外，电泳迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）分析的结果显示RbAp 48在体外与HIV-1 LTR结合。综上所述，这些发现表明，作为转录辅因子，RbAp 48可能作为一种有效的抗逆转录病毒防御。
Retinoblastoma binding protein 4 (RbAp48) is a histone chaperone which has been suggested to play a role in gene silencing. However, the role of RbAp48 in human immunodeficiency virus type 1 (HIV-1) infection and gene replication has not been determined to date, to the best of our knowledge. For this purpose, we demonstrated in the present study that RbAp48 expression was upregulated by HIV-1 infection, whereas the knockdown of RbAp48 promoted HIV infection and the production of virus particles. The ectopic expression of RbAp48 inhibited HIV-1 expression, and this inhibition correlated with a marked decrease in the expression of HIV-1 genomic RNA and various RNA transcripts. Further experiments to determine the mechanism responsible for the inhibitory effects of RbAp48 revealed that the ectopic expression of RbAp48 repressed HIV-1 long terminal repeat (LTR)-mediated basal transcription as well as TNF-α- and phorbol 12-myristate 13-acetate (PMA)‑activated transcription. Furthermore, the results of the electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis revealed that RbAp48 binds to the HIV-1 LTR in vitro. Taken together, these findings demonstrate that, as a transcriptional cofactor, RbAp48 is likely to act as a potent antiretroviral defense.