HIV-1 Vpr 通过增强 IKKα/β 的磷酸化来激活经典和非经典 NF-κB 通路。
HIV-1 Vpr activates both canonical and noncanonical NF-κB pathway by enhancing the phosphorylation of IKKα/β.
机构信息
Key Laboratory of Molecular Microbiology and Biotechnology, Ministry of Education and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin 300071, China.
出版信息
Virology. 2013 Apr 25;439(1):47-56. doi: 10.1016/j.virol.2013.01.020. Epub 2013 Feb 28.
The human immunodeficiency virus type I (HIV-1) Vpr plays an essential role in viral replication. A number of studies have reported that Vpr modulates the nuclear factor-κB (NF-κB) pathway. Yet, the reported effects of Vpr on NF-κB signaling are controversial. In this study, we investigate the interplay between Vpr and NF-κB pathway. We discover that HIV-1 infection elevates the phosphorylation of IκBα and p100, and that this increase is greatly reduced when a Vpr-negative HIV-1 is used for infection. Our data further show that Vpr regulates the activity of IKKα/β through interactions. In addition, Vpr modulates the phosphorylation of p65 and p100, suggesting that Vpr activates both canonical and noncanonical NF-κB pathway. Knock down of endogenous IKKα/β result in a decrease in Vpr-mediated NF-κB and HIV-1 LTR activation. Given that Vpr is present in HIV-1 particles, our data suggest that Vpr activates the NF-κB pathway immediately after HIV-1 entry.
人类免疫缺陷病毒 I 型 (HIV-1) Vpr 在病毒复制中起着至关重要的作用。许多研究报告称，Vpr 调节核因子-κB（NF-κB）途径。然而，Vpr 对 NF-κB 信号的影响存在争议。在这项研究中，我们研究了 Vpr 与 NF-κB 途径之间的相互作用。我们发现 HIV-1 感染会增加 IκBα 和 p100 的磷酸化，而当使用缺乏 Vpr 的 HIV-1 进行感染时，这种增加会大大减少。我们的数据进一步表明，Vpr 通过相互作用调节 IKKα/β 的活性。此外，Vpr 调节 p65 和 p100 的磷酸化，表明 Vpr 激活了经典和非经典 NF-κB 途径。内源性 IKKα/β 的敲低导致 Vpr 介导的 NF-κB 和 HIV-1 LTR 激活减少。鉴于 Vpr 存在于 HIV-1 颗粒中，我们的数据表明 Vpr 在 HIV-1 进入后立即激活 NF-κB 途径。
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