Virus proliferation mechanism by the monoubiquitin-dependent vesicular transport complex

尽管怀疑囊泡转运系统在病毒增殖中的重要性，但其背后的确切机制仍不清楚。在本研究中，我们研究了在病毒生命周期中对细胞表面受体进行分选的转运蛋白STAM1、STAM2和Hrs。小鼠巨细胞病毒（MCMV）的增殖被hr -depletion所抑制。由于MCMV的附着和进入不受Hrs的影响，我们接下来检查了即时早期基因，ie1的mrna与Hrs无关，没有显着差异。然而，出乎意料的是，IE1蛋白在hr耗竭后表现出明显的抑制作用。我发现IE1蛋白的一部分从细胞核进入细胞质，它位于核内体上。由于Hrs是一种内体蛋白，我们怀疑Hrs结合并分选Iel，导致溶酶体依赖性降解。总之，我们发现了囊泡分选蛋白Hrs在病毒转录因子调控中的新作用，这是正常病毒复制所必需的。

Although significance of the vesicular transport system in virus proliferation is suspected, precise mechanisms underlying it remains unknown. In this study, we investigated transport proteins STAM1, STAM2 and Hrs, all of which sort cell surface receptors, in virus life cycle. Mouse cytomegalovirus (MCMV) proliferation was decreased by the Hrs-depletion. Since MCMV attachment and entry left unaffected by Hrs, we next examined immediate early gene, ie1 mRNAs for ie1 showed no significant difference irrespective of Hrs. Unexpectedly, however, IE1 protein showed significant suppression by Hrs-depletion. I found that some portion of IE1 protein travels out of the nucleus into the cytoplasm, where it locates on the endosomes. Because Hrs is an endosomal protein, we suspect that Hrs binds and sorts Iel, leading to the lysosome dependent degradation. In conclusion, we found a novel role of a vesicular sorting protein Hrs in the regulation of a virus transcription factor, which is required for a normal virus replication.