Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China.
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
Virology. 2018 Aug;521:169-174. doi: 10.1016/j.virol.2018.06.008. Epub 2018 Jun 25.
HIV-1 hijacks host classical cargo nuclear transportation, or nonclassical pathways by directly interacting with importin-β family proteins or nucleoporins for efficient pre-integration complex (PIC) nuclear import. Recently, an N-terminal truncated form of nucleoporin Pom121c (601-987 aa) was reported to inhibit HIV-1 replication. In contrast, we found that HIV-1 replication was significantly decreased in 293T and TZM-b1 cells with siRNA-mediated Pom121 knockdown. Quantitative PCR indicated that viral replication was impaired at the step of cDNA nuclear import. Furthermore, we found that karyopherin-β1 (KPNB1), which belongs to the importin-β family, interacts with Pom121 and is involved in Pom121-mediated PIC nuclear import. Rescue experiment indicated that the FG-repeats and the following α-helix in Pom121 are required for its role in HIV-1 PIC nuclear import. Taken together, our results showed that full-length Pom121 enables efficient PIC nuclear import, and suggested that this process may rely on KPNB1 dependent classical cargo nuclear transportation way.
HIV-1 通过与 importin-β 家族蛋白或核孔蛋白直接相互作用来劫持宿主经典货物核运输或非经典途径，从而实现有效的前整合复合物（PIC）核导入。最近，报道了核孔蛋白 Pom121c 的 N 端截断形式（601-987 aa）可抑制 HIV-1 复制。相比之下，我们发现，用 siRNA 介导的 Pom121 敲低，可显著降低 293T 和 TZM-b1 细胞中的 HIV-1 复制。定量 PCR 表明，病毒复制在 cDNA 核导入步骤受到损害。此外，我们发现，属于 importin-β 家族的 karyopherin-β1（KPNB1）与 Pom121 相互作用，并参与 Pom121 介导的 PIC 核导入。挽救实验表明，Pom121 中的 FG 重复序列及其后续的α螺旋对于其在 HIV-1 PIC 核导入中的作用是必需的。总之，我们的研究结果表明全长 Pom121 可实现有效的 PIC 核导入，并提示该过程可能依赖于 KPNB1 依赖的经典货物核运输途径。
