Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico.
Molecular Virology, School of life Sciences, The Nottingham University, Nottingham NG72QL, UK.
Viruses. 2020 May 26;12(6):583. doi: 10.3390/v12060583.
During flavivirus infection, some viral proteins move to the nucleus and cellular components are relocated from the nucleus to the cytoplasm. Thus, the integrity of the main regulator of the nuclear-cytoplasmic transport, the nuclear pore complex (NPC), was evaluated during infection with dengue virus (DENV) and Zika virus (ZIKV). We found that while during DENV infection the integrity and distribution of at least three nucleoporins (Nup), Nup153, Nup98, and Nup62 were altered, during ZIKV infection, the integrity of TPR, Nup153, and Nup98 were modified. In this work, several lines of evidence indicate that the viral serine protease NS2B3 is involved in Nups cleavage. First, the serine protease inhibitors, TLCK and Leupeptin, prevented Nup98 and Nup62 cleavage. Second, the transfection of DENV and ZIKV NS2B3 protease was sufficient to inhibit the nuclear ring recognition detected in mock-infected cells with the Mab414 antibody. Third, the mutant but not the active (WT) protease was unable to cleave Nups in transfected cells. Thus, here we describe for the first time that the NS3 protein from flavivirus plays novel functions hijacking the nuclear pore complex, the main controller of the nuclear-cytoplasmic transport.
在黄病毒感染过程中，一些病毒蛋白转移到细胞核中，细胞成分从细胞核重新分布到细胞质中。因此，评估了登革热病毒（DENV）和寨卡病毒（ZIKV）感染过程中核孔复合体（NPC）这一主要核质转运调控因子的完整性。我们发现，虽然 DENV 感染过程中至少三种核孔蛋白（Nup），Nup153、Nup98 和 Nup62 的完整性和分布发生改变，但 ZIKV 感染时 TPR、Nup153 和 Nup98 的完整性发生改变。在这项工作中，有几条证据表明病毒丝氨酸蛋白酶 NS2B3 参与了 Nups 的切割。首先，丝氨酸蛋白酶抑制剂 TLCK 和亮肽素可阻止 Nup98 和 Nup62 的切割。其次，DENV 和 ZIKV NS2B3 蛋白酶的转染足以抑制用 Mab414 抗体在模拟感染细胞中检测到的核环识别。第三，突变但非活性（WT）蛋白酶不能切割转染细胞中的 Nups。因此，我们首次描述了黄病毒的 NS3 蛋白通过劫持核孔复合体这一核质转运的主要控制器，发挥新的功能。
