美国德克萨斯大学医学分校Ricardo Rajsbaum和Pei-Yong Shi研究组取得最新进展。他们发现包膜蛋白（E）泛素化驱动寨卡病毒的进入和发病。2020年7月8日出版的《自然》杂志发表了这项成果。
他们显示ZIKV的包膜蛋白（E）被E3泛素连接酶TRIM7通过Lys63（K63）连接的多聚泛素修饰。因此，ZIKV在Trim7−/−小鼠的大脑和生殖组织中复制效率较低。当ZIKV从特定细胞类型中释放时，泛素化E存在于ZIKV的感染性病毒颗粒中，并增强病毒的附着和进入细胞。
具体而言，K63连接的聚泛素链与宿主细胞的TIM1（也称为HAVCR1）受体直接相互作用，从而增强了病毒在体内进入脑组织和细胞中。缺乏泛素化的重组ZIKV突变体在人细胞和野生型小鼠中毒性减弱，而在活蚊子中则没有。针对K63连接的多泛素的单克隆抗体可特异性中和ZIKV，并降低小鼠的病毒血症。他们的结果表明ZIKV E的泛素化是病毒进入、嗜性和致病性的重要决定因素。
据了解，ZIKV属于黄病毒科，与其他引起人类疾病的病毒有关。与其他黄病毒不同，ZIKV感染可引起先天性神经系统疾病，并在生殖组织中有效复制。
附：英文原文
Title: Envelope protein ubiquitination drives entry and pathogenesis of Zika virus
Author: Maria I. Giraldo, Hongjie Xia, Leopoldo Aguilera-Aguirre, Adam Hage, Sarah van Tol, Chao Shan, Xuping Xie, Gail L. Sturdevant, Shelly J. Robertson, Kristin L. McNally, Kimberly Meade-White, Sasha R. Azar, Shannan L. Rossi, Wendy Maury, Michael Woodson, Holly Ramage, Jeffrey R. Johnson, Nevan J. Krogan, Marc C. Morais, Sonja M. Best, Pei-Yong Shi, Ricardo Rajsbaum
Issue&Volume: 2020-07-08
Abstract: Zika virus (ZIKV) belongs to the family Flaviviridae, and is related to other viruses that cause human diseases. Unlike other flaviviruses, ZIKV infection can cause congenital neurological disorders and replicates efficiently in reproductive tissues1,2,3. Here we show that the envelope protein (E) of ZIKV is polyubiquitinated by the E3 ubiquitin ligase TRIM7 through Lys63 (K63)-linked polyubiquitination. Accordingly, ZIKV replicates less efficiently in the brain and reproductive tissues of Trim7/ mice. Ubiquitinated E is present on infectious virions of ZIKV when they are released from specific cell types, and enhances virus attachment and entry into cells. Specifically, K63-linked polyubiquitin chains directly interact with the TIM1 (also known as HAVCR1) receptor of host cells, which enhances virus entry in cells as well as in brain tissue in vivo. Recombinant ZIKV mutants that lack ubiquitination are attenuated in human cells and in wild-type mice, but not in live mosquitoes. Monoclonal antibodies against K63-linked polyubiquitin specifically neutralize ZIKV and reduce viraemia in mice. Our results demonstrate that the ubiquitination of ZIKV E is an important determinant of virus entry, tropism and pathogenesis.
DOI: 10.1038/s41586-020-2457-8
Source: https://www.nature.com/articles/s41586-020-2457-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
