A Network of Protein Interactions around the Herpes Simplex Virus Tegument Protein VP22
A Network of Protein Interactions around the Herpes Simplex Virus Tegument Protein VP22
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DOI：
10.1128/jvi.01913-12
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发表时间：
2012-12-01
影响因子：
5.4
通讯作者：
Elliott, Gillian
中科院分区：
文献类型：
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作者：
Maringer, Kevin;Stylianou, Julianna;Elliott, Gillian
疱疹病毒被膜的组装尚不清楚，但被认为涉及外层被膜蛋白和包膜糖蛋白的细胞质结构域之间的相互作用。在这里，我们提出了在单纯疱疹病毒1型(HSV-1)感染细胞中发现的多组分糖蛋白-被膜复合体的详细特征。我们证明了被膜蛋白VP22在糖蛋白E(GE)和糖蛋白M(GM)之间架起了一个复合体。糖蛋白I(GI)是GE的已知结合伙伴，也被招募到GE-VP22-GM复合体中，但它的形成并不是必需的。排除糖蛋白GB和GD以及VP22的主要结合伙伴S的VP16表明，病毒粒子组分的招募到该复合体是具有高度选择性的。需要VP22才能包装到病毒粒子中的即刻早期蛋白ICP0也以VP22依赖的方式组装到这个GE-VP22-GM-GI复合体中。虽然在没有Ge或GM的情况下，可以形成含有VP22和ICP0的亚复合体，但最佳的复合体形成需要这两种糖蛋白。此外，为了形成复杂的结构，VP22或ICP0包装到病毒粒子中并不单独需要这两种糖蛋白，但Ge和GM的缺失大大减少了VP22和ICP0的组装。GE和GM的双重缺失也会导致斑块尺寸变小，病毒产量减少，二次包膜缺陷，类似于以前显示的伪狂犬病病毒的表型。因此，我们认为最佳的GE-VP22-GM-GI-ICP0复合体的形成与有效的病毒形态发生和传播有关。这些数据让人们对鲜为人知的被膜获取过程有了新的见解。
Assembly of the herpesvirus tegument is poorly understood but is believed to involve interactions between outer tegument proteins and the cytoplasmic domains of envelope glycoproteins. Here, we present the detailed characterization of a multicomponent glycoprotein-tegument complex found in herpes simplex virus 1 (HSV-1)-infected cells. We demonstrate that the tegument protein VP22 bridges a complex between glycoprotein E (gE) and glycoprotein M(gM). Glycoprotein I (gI), the known binding partner of gE, is also recruited into this gE-VP22-gM complex but is not required for its formation. Exclusion of the glycoproteins gB and gD and VP22's major binding partner VP16 demonstrates that recruitment of virion components into this complex is highly selective. The immediate-early protein ICP0, which requires VP22 for packaging into the virion, is also assembled into this gE-VP22-gM-gI complex in a VP22-dependent fashion. Although subcomplexes containing VP22 and ICP0 can be formed when either gE or gM are absent, optimal complex formation requires both glycoproteins. Furthermore, and in line with complex formation, neither of these glycoproteins is individually required for VP22 or ICP0 packaging into the virion, but deletion of gE and gM greatly reduces assembly of both VP22 and ICP0. Double deletion of gE and gM also results in small plaque size, reduced virus yield, and defective secondary envelopment, similar to the phenotype previously shown for pseudorabies virus. Hence, we suggest that optimal gE-VP22-gM-gI-ICP0 complex formation correlates with efficient virus morphogenesis and spread. These data give novel insights into the poorly understood process of tegument acquisition.