The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR
The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR
复制标题
CREB 调节转录辅激活因子 2 通过阻止 RNA Pol II 与 HIV-1 LTR 结合来抑制 HIV-1 转录
DOI：
10.1007/s12250-021-00363-1
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发表时间：
2021-03-15
影响因子：
5.5
通讯作者：
Cen, Shan
中科院分区：
文献类型：
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作者：
Ma, Ling;Chen, Shumin;Cen, Shan
creb调控的转录共激活因子（crtc），包括CRTC1、CRTC2和CRTC3，可增强creb靶向基因的转录。除了调节宿主基因表达以响应cAMP外，crtc还会增加几种病毒的感染。虽然人类免疫缺陷病毒1型（HIV-1）长末端重复序列（LTR）启动子含有cAMP应答元件，cAMP通路的激活促进HIV-1转录，但crtc是否对HIV-1转录和HIV-1感染有任何影响尚不清楚。在这里，我们报道了CRTC2的表达被HIV-1感染诱导，但CRTC2抑制HIV-1感染并降低病毒RNA的表达。机制研究表明，CRTC2抑制了HIV-1 LTR的转录，并减少了LTR上RNA Pol II的占用，而与CREB无关。重要的是，CRTC2抑制潜伏HIV-1的激活。总之，这些数据表明，在对HIV-1感染的反应中，细胞增加CRTC2的表达，从而抑制HIV-1基因的表达，并可能在驱动HIV-1进入潜伏期中发挥作用。
The CREB-regulated transcriptional co-activators (CRTCs), including CRTC1, CRTC2 and CRTC3, enhance transcription of CREB-targeted genes. In addition to regulating host gene expression in response to cAMP, CRTCs also increase the infection of several viruses. While human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter harbors a cAMP response element and activation of the cAMP pathway promotes HIV-1 transcription, it remains unknown whether CRTCs have any effect on HIV-1 transcription and HIV-1 infection. Here, we reported that CRTC2 expression was induced by HIV-1 infection, but CRTC2 suppressed HIV-1 infection and diminished viral RNA expression. Mechanistic studies revealed that CRTC2 inhibited transcription from HIV-1 LTR and diminished RNA Pol II occupancy at the LTR independent of its association with CREB. Importantly, CRTC2 inhibits the activation of latent HIV-1. Together, these data suggest that in response to HIV-1 infection, cells increase the expression of CRTC2 which inhibits HIV-1 gene expression and may play a role in driving HIV-1 into latency.