Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.
Division of HIV/AIDS, The Second Affiliated Hospital of Soochow University, Soochow, China.
PLoS One. 2021 Dec 29;16(12):e0261971. doi: 10.1371/journal.pone.0261971. eCollection 2021.
MicroRNAs (miRNAs) are important molecules that mediate virus-host interactions, mainly by regulating gene expression via gene silencing. Here, we demonstrated that HIV-1 infection upregulated miR-210-5p in HIV-1-inoculated cell lines and in the serum of HIV-1-infected individuals. Luciferase reporter assays and western blotting confirmed that a target protein of miR-210-5p, TGIF2, is regulated by HIV-1 infection. Furthermore, HIV-1 Vpr protein induced miR-210-5p expression. The use of a miR-210-5p inhibitor and TGIF2 overexpression showed that Vpr upregulated miR-210-5p and thereby downregulated TGIF2, which might be one of the mechanisms used by Vpr to induce G2 arrest. Moreover, we identified a transcription factor, NF-κB p50, which upregulated miR-210-5p in response to Vpr protein. In conclusion, we identified a mechanism whereby miR-210-5p, which is induced upon HIV-1 infection, targets TGIF2. This pathway was initiated by Vpr protein activating NF-κB p50, which promoted G2 arrest. These alterations orchestrated by miRNA provide new evidence on how HIV-1 interacts with its host during infection and increase our understanding of the mechanism by which Vpr regulates the cell cycle.
微小 RNA（miRNA）是一种重要的分子，通过基因沉默调节基因表达，从而介导病毒-宿主相互作用。在这里，我们证明 HIV-1 感染可上调 HIV-1 接种细胞系和 HIV-1 感染者血清中的 miR-210-5p。荧光素酶报告基因检测和 Western blot 证实，miR-210-5p 的一个靶蛋白 TGIF2 受 HIV-1 感染调控。此外，HIV-1 Vpr 蛋白诱导 miR-210-5p 的表达。使用 miR-210-5p 抑制剂和 TGIF2 过表达表明，Vpr 上调 miR-210-5p，从而下调 TGIF2，这可能是 Vpr 诱导 G2 期阻滞的机制之一。此外，我们鉴定了一个转录因子 NF-κB p50，它可响应 Vpr 蛋白而上调 miR-210-5p。总之，我们确定了一种机制，即 HIV-1 感染后诱导的 miR-210-5p 靶向 TGIF2。该途径由 Vpr 蛋白激活 NF-κB p50 引发，从而促进 G2 期阻滞。这些 miRNA 协调的改变为 HIV-1 在感染过程中与宿主相互作用提供了新的证据，并加深了我们对 Vpr 调控细胞周期的机制的理解。
