Trafficking of Proteins to the Herpes Simplex Tegument

所有疱疹病毒都具有一层称为外皮的蛋白质层，该层排列在内表面 他们的信封。在初级阶段， 二次减数分裂时在细胞质中。这些皮层是 然而，形态学上不同，很少有人知道它们的分子组成如何不同。 此外，皮层蛋白与膜结合的机制， 整合到组装的HSV颗粒中的蛋白质是知之甚少的。 我们已经在VHS的氨基端鉴定了一个42个氨基酸的膜靶向基序， 皮层成分，是一个重要的神经毒力决定因素。这种膜分选基序是 也足以将GFP报道基因导入HSV颗粒。此外，我们还表明， 与包膜糖蛋白gH的胞质尾区结合。本提案的目的是剖析 vhs氨基末端靶向膜的分子细节，测试了gH在这一过程中的作用。 处理和检查的性质vhs在核周HSV粒子。我们还使用新的 开发了研究核周HSV的一般组成和功能的方法 颗粒，检查VHS对核周病毒体的靶向作用，并比较VHS的包膜和被膜。 这些特征不佳的颗粒与成熟病毒体的颗粒相比较。

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.