导 读
近期，苏州大学生物医学研究院董春升教授在《Virology》上发表了题为 “The transmembrane nucleoporin Pom121 ensures efficient HIV-1 pre-integration complex nuclear import”的研究论文，研究报道了跨膜核孔蛋白Pom121在HIV-1 PIC入核过程中的作用。
结果速览
人I型免疫缺陷病毒（HIV-1）属于逆转录病毒科慢病毒属，病毒能够在非分裂细胞中复制有赖于病毒整合前复合物（PIC）的入核运输，然后整合到宿主细胞的基因组上。Pom121是脊椎动物最为保守的跨膜核孔蛋白之一，已知Pom121是细胞有丝分裂后期核孔复合体组装过程中被早期募集的蛋白，并已被证明对分裂间期核膜组装形成发挥着重大作用。然而Pom121对于HIV-1 PIC入核功能作用还少有报道。该论文首次发现全长的Pom121能增加HIV-1 PIC的入核效率，促进病毒复制，为HIV-1 PIC入核转运增添了新的机制。
Fig. 1Pom121 supports HIV-1 replication.
先前研究报道N端600氨基酸缺失的Pom121能够抑制HIV-1的复制。在此项研究中，通过luciferase病毒感染试验及对病毒基因组入核指标2-LTR的检测，发现下调Pom121可以减少PIC的入核，从而抑制病毒的感染。进一步实验表明，Pom121可以与上游核转运蛋白karyopherin-β1相互作用，介导的PIC入核转运，并且Pom121的FG结构域对于PIC的入核转运功能是必需的，该结果首次鉴定了Pom121在HIV-1PIC入核过程中的重要作用。
Fig. 2：Pom121 FG-domain is required for HIV-1 cDNA nuclear import.
结 语
该论文首次发现全长的Pom121能增加HIV-1 PIC的入核效率，促进病毒复制，为HIV-1 PIC入核转运增添了新的机制。郭晶为该论文的第一作者，参与该论文的还有刘贤贤，武传建等。苏州大学董春升教授和熊思东教授为该论文的并列通讯作者。该研究由国家自然科学基金（81101257, 31470848, 31670898 ，31470880），病毒学国家重点实验室开放研究基金项目(2017IOV003)等资金资助。
Abstract
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.
Highlights
Pom121 promotes HIV-1 replication in vitro.
Pom121 facilitates HIV-1 PIC nuclear import.
FG-repeats domain in Pom121 is required for PIC nuclear import.
Pom121 mediated PIC nuclear import is KPNB1 dependent.
DOI
10.1016/j.virol.2018.06.008
本期编辑：hantavirus |
