Nelson Lisa M, Rose Robert C, Moroianu Junona
Biology Department, Boston College, Chestnut Hill, Massachusetts 02467, USA.
J Biol Chem. 2002 Jun 28;277(26):23958-64. doi: 10.1074/jbc.M200724200. Epub 2002 Apr 23.
During the late phase of human papillomavirus (HPV) infection, the L1 major capsid proteins enter the nuclei of host epithelial cells and, together with the L2 minor capsid proteins, assemble the replicated viral DNA into virions. We investigated the nuclear import of the L1 major capsid protein of high risk HPV16. When digitonin-permeabilized HeLa cells were incubated with HPV16 L1 capsomeres, the L1 protein was imported into the nucleus in a receptor-mediated manner. HPV16 L1 capsomeres formed complexes with Kap alpha2beta1 heterodimers via interaction with Kap alpha2. Accordingly, nuclear import of HPV16 L1 capsomeres was mediated by Kap alpha2beta1 heterodimers, required RanGDP and free GTP, and was independent of GTP hydrolysis. Remarkably, HPV16 L1 capsomeres also interacted with Kap beta2 and binding of RanGTP to Kap beta2 did not dissociate the HPV16 L1.Kap beta2 complex. Significantly, HPV16 L1 capsomeres inhibited the nuclear import of Kap beta2 and of a Kap beta2-specific M9-containing cargo. These data suggest that, during the productive stage of infection, while the HPV16 L1 major capsid protein enters the nucleus via the Kap alpha2beta1-mediated pathway to assemble the virions, it also inhibits the Kap beta2-mediated nuclear import of host hnRNP A1 protein and, in this way, favors virion formation.
在人乳头瘤病毒（HPV）感染的后期，L1主要衣壳蛋白进入宿主上皮细胞核，并与L2次要衣壳蛋白一起将复制的病毒DNA组装成病毒颗粒。我们研究了高危型HPV16的L1主要衣壳蛋白的核输入。当用洋地黄皂苷通透处理的HeLa细胞与HPV16 L1衣壳粒一起孵育时，L1蛋白以受体介导的方式被输入细胞核。HPV16 L1衣壳粒通过与Kap α2相互作用与Kap α2β1异二聚体形成复合物。因此，HPV16 L1衣壳粒的核输入由Kap α2β1异二聚体介导，需要RanGDP和游离GTP，且不依赖于GTP水解。值得注意的是，HPV16 L1衣壳粒也与Kap β2相互作用，并且RanGTP与Kap β2的结合不会使HPV16 L1-Kap β2复合物解离。重要的是，HPV16 L1衣壳粒抑制了Kap β2以及一种含Kap β2特异性M9的货物的核输入。这些数据表明，在感染的增殖阶段，当HPV16 L1主要衣壳蛋白通过Kap α2β1介导的途径进入细胞核以组装病毒颗粒时，它也抑制了宿主hnRNP A1蛋白的Kap β2介导的核输入，并且以这种方式有利于病毒颗粒的形成。
