Cellular RelB interacts with the transactivator Tat and enhance HIV-1 expression.

Cellular RelB interacts with the transactivator Tat and enhance HIV-1 expression.
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细胞 RelB 与反式激活因子 Tat 相互作用并增强 HIV-1 表达

DOI:
10.1186/s12977-018-0447-9
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发表时间:
2018-09-21
期刊:
影响因子:
3.3
通讯作者:
Qiao W
Qiao W
中科院分区:
医学2区
文献类型:
--
作者:
Wang M;Yang W;Chen Y;Wang J;Tan J;Qiao W

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背景人类免疫缺陷病毒1型(human immunodeficiency virus type 1,HIV-1)达特蛋白在HIV-1基因转录过程中起重要作用。达特通过与HIV-1长末端重复序列(LTR)中的反式激活反应区(TAR)元件和其它顺式元件直接相互作用,反式激活LTR指导的基因表达。TAR独立的Tat介导的LTR反式激活是由几个主机factors调制,但其机制还不完全understood.ResultsHere,我们报告,达特与RelB的Rel同源结构域通过其核心区域相互作用。此外,RelB显著增加Tat介导的HIV-1 LTR转录和病毒基因表达,这与TAR无关。达特和RelB都被募集到HIV-1启动子,其中RelB促进达特募集到病毒LTR。NF-κB元件是达特和RelB在LTR上积累的关键。RelB的敲除减少了RNA聚合酶II在LTR上的积累,并降低了HIV-1基因的转录。总之,我们的数据表明,RelB有助于HIV-1 transactivation.ConclusionsOur结果表明,RelB相互作用与达特和增强TAR非依赖性激活的HIV-1 LTR启动子,这增加了新的见解的多层机制的达特在调节HIV-1的基因表达。
BackgroundHuman immunodeficiency virus type 1 (HIV-1) Tat protein plays an essential role in HIV-1 gene transcription. Tat transactivates HIV-1 long terminal repeat (LTR)-directed gene expression through direct interactions with the transactivation-responsive region (TAR) element and otherciselements in the LTR. The TAR-independent Tat-mediated LTR transactivation is modulated by several host factors, but the mechanism is not fully understood.ResultsHere, we report that Tat interacts with the Rel homology domain of RelB through its core region. Furthermore, RelB significantly increases Tat-mediated transcription of the HIV-1 LTR and viral gene expression, which is independent of the TAR. Both Tat and RelB are recruited to the HIV-1 promoter, of which RelB facilitates the recruitment of Tat to the viral LTR. The NF-κB elements are key to the accumulation of Tat and RelB on the LTR. Knockout of RelB reduces the accumulation of RNA polymerase II on the LTR, and decreases HIV-1 gene transcription. Together, our data suggest that RelB contributes to HIV-1 transactivation.ConclusionsOur results demonstrate that RelB interacts with Tat and enhances TAR-independent activation of HIV-1 LTR promoter, which adds new insights into the multi-layered mechanisms of Tat in regulating the gene expression of HIV-1.
DOI: 10.3390/v9040067
发表时间: 2017-04-01
期刊: Viruses
影响因子: --
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影响因子: 11.1
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