Nck- 和 N-WASP 依赖性肌动蛋白为基础的运动在不同的脊椎动物痘病毒中是保守的。

Nck- and N-WASP-dependent actin-based motility is conserved in divergent vertebrate poxviruses.

机构信息

Cell Motility Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

出版信息

Cell Host Microbe. 2009 Dec 17;6(6):536-50. doi: 10.1016/j.chom.2009.10.011.

DOI:10.1016/j.chom.2009.10.011

PMID:20006842

Abstract

Vaccinia virus enhances its cell-to-cell spread by stimulating actin polymerization via Src- and Abl-mediated phosphorylation of the highly conserved orthopoxvirus protein A36. The Yatapoxvirus, Yaba-like disease virus (YLDV), also induces actin polymerization, although it lacks an obvious A36 ortholog. We found that the YLDV protein YL126 can functionally replace A36 to promote Nck- and N-WASP-dependent actin polymerization. At least five phosphorylated tyrosines in YL126, rather than a single residue as in A36, are able to recruit Nck to promote actin polymerization. As is the case for A36, YL126-mediated actin tail formation is enhanced by the recruitment of Grb2 via a single phosphorylated tyrosine in YL126. Furthermore, highly divergent YL126 orthologs in Yaba monkey tumor, lumpy skin disease, Shope fibroma, myxoma, and swine and squirrel poxviruses also stimulate Nck- and N-WASP-dependent actin polymerization, suggesting that actin-based motility represents a common mechanism to enhance the cell-to-cell spread of vertebrate poxviruses.

摘要

痘病毒通过 Src 和 Abl 介导的高度保守的正痘病毒蛋白 A36 的磷酸化来刺激肌动蛋白聚合，从而增强其细胞间传播。Yatapoxvirus（雅塔痘病毒），即 Yaba 样疾病病毒（YLDV），也会诱导肌动蛋白聚合，尽管它缺乏明显的 A36 直系同源物。我们发现 YLDV 蛋白 YL126 可以替代 A36 发挥功能，促进 Nck 和 N-WASP 依赖性肌动蛋白聚合。YL126 中至少有五个磷酸化的酪氨酸残基，而不是 A36 中的单个残基，能够募集 Nck 以促进肌动蛋白聚合。与 A36 一样，YL126 通过 YL126 中的一个磷酸化酪氨酸募集 Grb2，从而增强 A36 介导的肌动蛋白尾形成。此外，在 Yaba 猴肿瘤、块状皮肤病、Shope 纤维瘤、粘液瘤以及猪和松鼠痘病毒中高度分化的 YL126 直系同源物也刺激 Nck 和 N-WASP 依赖性肌动蛋白聚合，这表明基于肌动蛋白的运动代表了增强脊椎动物痘病毒细胞间传播的共同机制。