SV40VP2 and VP3 insertion into ER membranes is controlled by the capsid protein VP1: Implications for DNA translocation out of the ER
SV40VP2 and VP3 insertion into ER membranes is controlled by the capsid protein VP1: Implications for DNA translocation out of the ER
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DOI：
10.1016/j.molcel.2006.11.001
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发表时间：
2006-12-28
期刊：
影响因子：
16
通讯作者：
Hebert, Daniel N.
中科院分区：
文献类型：
--
作者：
Daniels, Robert;Rusan, Nasser M.;Hebert, Daniel N.
无包膜病毒如猿猴病毒40（SV40）利用已建立的细胞途径内化和运输到其渗透部位。通过分析不表达VP2或VP3的突变体SV40基因组，我们发现这些结构蛋白执行由VP1调节的基本功能。VP2显著增强了SV40颗粒与宿主细胞的结合，而VP3则起下游作用。VP2和VP3均整合到内质网（ER）膜上。与VP1五聚体的关联阻止了它们的ER膜整合，表明VP1通过指导它们在颗粒和ER膜之间的定位来控制VP2和VP3的功能。这些发现表明了一种模型，其中VP2有助于细胞结合。在内质网腔内衣壳解体后，VP3，可能还有VP2，寡聚化并整合到内质网膜中，可能产生一种病毒孔蛋白，有助于病毒DNA转运出内质网。
Nonenveloped viruses such as Simian Virus 40 (SV40) exploit established cellular pathways for internalization and transport to their site of penetration. By analyzing mutant SV40 genomes that do not express VP2 or VP3, we found that these structural proteins perform essential functions that are regulated by VP1. VP2 significantly enhanced SV40 particle association with the host cell, while VP3 functioned downstream. VP2 and VP3 both integrated posttranslationally into the endoplasmic reticulum (ER) membrane. Association with VP1 pentamers prevented their ER membrane integration, indicating that VP1 controls the function of VP2 and VP3 by directing their localization between the particle and the ER membrane. These findings suggest a model in which VP2 aids in cell binding. After capsid disassembly within the ER lumen, VP3, and perhaps VP2, oligomerizes and integrates into the ER membrane, potentially creating a viroporin that aids in viral DNA transport out of the ER.