Trafficking of Proteins to the Herpes Simplex Tegument

蛋白质运输到单纯疱疹皮膜

• 批准号: 7931176
• 负责人: DUNCAN W. WILSON
• 金额: $ 58.06万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-26 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7931176
• 关键词: Address; Amino Acids; Automobile Driving; Binding; Biochemical; Biochemistry; Capsid; Cell membrane; Cells; Cellular Membrane; Cytoplasm; Cytoplasmic Tail; Disease; Glycoproteins; Herpes Simplex Infections; Herpesviridae; In Vitro; Intracellular Membranes; Left; Lipids; Mass Spectrum Analysis; Mediating; Membrane; Membrane Protein Traffic; Methodology; Modeling; Molecular; Nature; Nuclear; Nuclear Inner Membrane; Pathway interactions; Process; Property; Proteins; Protocols documentation; Reporter; Role; Scaffolding Protein; Simplexvirus; Sorting - Cell Movement; Structure; Surface; Tail; Techniques; Testing; Virion; Virus Assembly; Western Blotting; env Gene Products; neurovirulence; particle; protein complex; protein transport; research study

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.

所有疱疹病毒都具有称为外皮的蛋白质层，位于内表面 他们的信封。皮层是在初级阶段在内核膜处获得的 包膜，以及二次包膜期间的细胞质中。这些外皮层是 然而，它们在形态上不同，但人们对它们的分子组成有何不同知之甚少。 此外，外皮蛋白与膜结合的机制和 对于如何整合到组装的 HSV 颗粒中，人们知之甚少。 我们在 vhs 的氨基末端鉴定了一个 42 个氨基酸的膜靶向基序， 被膜成分是重要的神经毒力决定因素。该膜分选基序是 也足以将 GFP 报告基因引导至 HSV 颗粒中。此外，我们还证明了 vhs 与包膜糖蛋白 gH 的细胞质尾部结合。该提案的目的是剖析 vhs 氨基末端膜靶向的分子细节，测试了 gH 在此过程中的作用 过程并检查核周 HSV 颗粒中 vhs 的性质。我们也用新的 开发了研究核周 HSV 的一般组成和功能的方法 颗粒，检查 vhs 对核周病毒颗粒的靶向，并比较包膜和外皮 这些特征不明的颗粒与成熟病毒颗粒的颗粒。