Laboratory of Immunoinfectivology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Virology. 2018 Oct;523:121-128. doi: 10.1016/j.virol.2018.07.031. Epub 2018 Aug 14.
The HIV-1 accessory protein Vpr displays various activities that can favor viral replication such as G cell cycle arrest. Vpr also modulates host gene expression, although this property is poorly characterized. Here, we investigated the effect of Vpr on L-selectin (CD62L), which crucially controls leukocytes circulation and generation of immune responses against pathogens. We report that Vpr up-regulates CD62L mRNA level when individually expressed in Jurkat T cells as well as during HIV-1 infection of primary CD4 T cells. Vpr mutant analysis and use of inhibitors suggest that the effect of Vpr on CD62L occurs independently of G arrest but requires activation of the ATR kinase. Yet, induction of CD62L expression by Vpr is contrasted by down-regulation of CD62L protein by Nef that, together with Vpu, induces a net reduction of cell-surface CD62L on HIV-1-infected cells, which may impact viral spread and evasion of immune responses.
HIV-1 辅助蛋白 Vpr 具有多种促进病毒复制的活性，如 G 期细胞周期阻滞。Vpr 还能调节宿主基因表达，尽管其性质尚未得到充分描述。在这里，我们研究了 Vpr 对 L-选择素（CD62L）的影响，CD62L 对白细胞循环和针对病原体的免疫反应的产生至关重要。我们报告说，Vpr 在单独表达于 Jurkat T 细胞中以及在 HIV-1 感染原代 CD4 T 细胞期间，均能上调 CD62L mRNA 水平。Vpr 突变分析和抑制剂的使用表明，Vpr 对 CD62L 的作用不依赖于 G 期阻滞，但需要激活 ATR 激酶。然而，Vpr 诱导 CD62L 表达与 Nef 下调 CD62L 蛋白形成对比，Nef 与 Vpu 一起导致 HIV-1 感染细胞表面 CD62L 的净减少，这可能影响病毒的传播和免疫反应的逃避。
