Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Viruses. 2021 Nov 19;13(11):2308. doi: 10.3390/v13112308.
Human immunodeficiency virus type 1 (HIV-1) modulates the host cell cycle. The HIV-1 accessory protein Vpr arrests the cell cycle at the G2 phase in dividing cells, and the ability of Vpr to induce G2 arrest is well conserved among primate lentiviruses. Additionally, Vpr-mediated G2 arrest likely correlates with enhanced HIV-1 infection in monocyte-derived macrophages. Here, we screened small-interfering RNA to reveal candidates that suppress Vpr-induced G2 arrest and identified Huntingtin-interacting protein 1 (HIP1) required for efficient G2 arrest. Interestingly, HIP1 was not essential for Vpr-induced DNA double-strand breaks, which are required for activation of the DNA-damage checkpoint and G2 arrest. Furthermore, HIP1 knockdown suppressed HIV-1 infection in monocyte-derived macrophages. This study identifies HIP1 as a factor promoting Vpr-induced G2 arrest and HIV-1 infection in macrophages.
人类免疫缺陷病毒 1 型（HIV-1）调节宿主细胞周期。HIV-1 辅助蛋白 Vpr 在分裂细胞中将细胞周期阻滞在 G2 期，而 Vpr 诱导 G2 期阻滞的能力在灵长类慢病毒中得到了很好的保守。此外，Vpr 介导的 G2 期阻滞可能与单核细胞来源的巨噬细胞中 HIV-1 感染的增强相关。在这里，我们筛选了小干扰 RNA，以揭示抑制 Vpr 诱导的 G2 期阻滞的候选物，并鉴定了用于有效 G2 期阻滞的 Huntingtin 相互作用蛋白 1（HIP1）。有趣的是，HIP1 对于 Vpr 诱导的 DNA 双链断裂不是必需的，DNA 损伤检查点的激活和 G2 期阻滞需要 DNA 双链断裂。此外，HIP1 敲低抑制了单核细胞来源的巨噬细胞中的 HIV-1 感染。本研究将 HIP1 鉴定为促进 Vpr 诱导的 G2 期阻滞和巨噬细胞中 HIV-1 感染的因素。
