Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection.
Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection.
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DOI：
10.1128/jvi.02196-16
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发表时间：
2017-01-15
影响因子：
5.4
通讯作者：
Crump CM
中科院分区：
文献类型：
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作者：
Albecka A;Owen DJ;Ivanova L;Brun J;Liman R;Davies L;Ahmed MF;Colaco S;Hollinshead M;Graham SC;Crump CM
疱疹病毒的被膜是位于核衣壳和病毒粒子包膜之间的高度复杂的结构层。被膜蛋白在复制和传播过程中既发挥结构功能又发挥调节功能，但其中许多蛋白的相互作用和功能尚不清楚。在这里，我们重点研究单纯疱疹病毒1型(HSV-1)的两种被蛋白，pUL7和pUL51，它们在所有其他疱疹病毒中都有同源基因。我们现在已经确定HSV-1 pUL7和pUL51形成稳定的直接的蛋白质相互作用，它们的表达水平依赖于彼此的存在，并且它们在感染细胞中作为一个复合体发挥作用。我们证明了pUL7-pUL51复合体的表达对于HSV-1的有效组装和斑块形成是重要的。此外，我们还发现，在没有其他病毒蛋白的情况下，pUL7-pUL51复合体定位于两个感染细胞的质膜上的焦点粘连。PUL7-pUL51的表达对于稳定感染细胞的局部黏附和维持细胞形态是重要的，并且缺乏pUL7和/或pUL51的病毒感染的细胞比感染野生型HSV-1的细胞更快地聚集。我们的数据表明，除了先前报道的pUL51在病毒组装和传播中的功能外，pUL7-pUL51复合体对于通过调节焦点黏附复合体的活性来维持感染细胞与周围细胞的附着是重要的。重要性疱疹病毒科是一个非常成功的人类和动物病原体大家族。这些病毒的病毒粒子由许多不同的蛋白质组成，其中大部分包含在被膜内，被膜是病毒颗粒内核衣壳和包膜之间的一个复杂的结构层。被膜蛋白在组装病毒颗粒以及修饰宿主细胞以促进病毒复制和传播方面具有重要作用。然而，对许多被膜蛋白在病毒复制过程中的功能知之甚少。我们的研究重点是单纯疱疹病毒1型的两种被膜蛋白，它们在所有疱疹病毒中都是保守的：pUL7和pUL51。我们证明了这些蛋白质直接相互作用并形成一个对病毒组装和宿主细胞形态调节都很重要的功能复合体。此外，我们首次发现，这些保守的疱疹病毒被膜蛋白除了定位于感染细胞内的细胞质近核膜外，还定位于局部粘连。
The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes. IMPORTANCE Herpesviridae is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins during virus replication. Our study focuses on two tegument proteins from herpes simplex virus 1 that are conserved in all herpesviruses: pUL7 and pUL51. We demonstrate that these proteins directly interact and form a functional complex that is important for both virus assembly and modulation of host cell morphology. Further, we identify for the first time that these conserved herpesvirus tegument proteins localize to focal adhesions in addition to cytoplasmic juxtanuclear membranes within infected cells.