Trafficking of Proteins to the Herpes Simplex Tegument

所有疱疹病毒的内表面都有一层称为被膜的蛋白质层 从他们的信封里。原发灶在内核膜上均可获得被膜 二次包膜时在细胞质内。这些覆盖层是 然而，在形态上截然不同的，人们对它们的分子组成有何不同知之甚少。 此外，被膜蛋白与膜结合的机制以及 被整合到组装的HSV粒子中的人还知之甚少。 我们已经在VHS的氨基末端确定了一个42个氨基酸的膜靶向基序，a 外皮成分，是重要的神经毒性决定因素。这个膜分选主题是 也足以引导GFP记者进入HSV粒子。此外，我们已经证明，VHS 与包膜糖蛋白Gh的细胞质尾部结合。这项提案的目的是剖析 VHS氨基末端靶向膜的分子细节，测试GH在这方面的作用 过程，并检查了核周HSV粒子中VHS的性质。我们也使用新的 开发了研究核周单纯疱疹病毒一般组成和功能的方法 颗粒，检测VHS对核周病毒粒子的靶向性，并比较包膜和被膜 这些特征不佳的粒子与成熟的病毒粒子相同。

All Herpes viruses possess a proteinaceous layer termed tegument which lines the inner surface of their envelope. Tegument is acquired both at the inner nuclear membrane during primary envelopment, and in the cytoplasm during secondary envelopment. These tegument layers are morphologically distinct, however, little is known of how their molecular compositions differ. Furthermore, the mechanisms by which tegument proteins become bound to membranes and incorporated into the assembling HSV particle are poorly understood. We have identified a 42 amino acid membrane targeting motif in the amino terminus of vhs, a tegument component that is an important neurovirulence determinant. This membrane sorting motif is also sufficient to direct a GFP reporter into the HSV particle. Furthermore, we have shown that vhs binds to the cytoplasmic tail of the envelope glycoprotein gH. The aims of this proposal dissect the molecular details of membrane targeting by the amino terminus of vhs, tests the role of gH in this process and examines the nature of vhs in the perinuclear HSV particle. We also use newly developed methodologies to investigate the general composition and function of the perinuclear HSV particle, examine targeting of vhs to the perinuclear virion and compare the envelope and tegument of these poorly characterized particles with those of mature virions.