MECHANISM OF PH INDEPENDENT HSV ENTRY

描述：目前的建议将探讨疱疹的手段， 单纯病毒I型（HSV-1）通过pH非依赖性机制进入细胞。 申请人先前发现了对HSV-1难治的细胞系 但当感染性DNA被转染时，它可以复制HSV-1。 利用HeLa cDNA克隆文库转染， B5基因是在申请人的实验室中发现的。这个克隆人是 与最近发现的人类HVEM基因不同。研究 这里概述的将集中在这个基因的特征及其 作为病毒进入的受体。该项目的具体目标是： 1)表征B5的结构和组织分布， 准备功能分析工具，包括稳定转染的细胞 系和抗体; 2）确定B5在HSV进入中的功能， 通过评估稳定的结合、渗透和非渗透性， 在HSV-1进入期间的涂层。还将进行调查， 确定B5是否影响HSV-1传播，是否与 配体，以及它是否与HVEM相关; 3）检查B5是否以及如何 与病毒和细胞蛋白相互作用以介导HSV进入， 膜融合

DESCRIPTION: The present proposal will explore the means by which herpes simplex virus type I (HSV-1) enters cells by pH independent mechanisms. The applicant previous discovered a cell line that is refractory to HSV-1 entry, but which can replicate HSV-1 when infectious DNA is transfected. Utilizing transfection with libraries of HeLa cDNA clones, a novel human gene, B5 was discovered in the applicant's laboratory. This clone is different from the recently discovered human HVEM gene. The studies outlined here will center on the characterization of this gene and its role as a receptor for viral entry. The specific aims of the project are: 1) to characterize the structure and tissue distribution of B5 and to prepare tools for functional analysis including stably transfected cell lines and antibodies; 2) to determine the function of B5 in HSV entry, spread and infection by assessing stable binding, penetration and un- coating during entry of HSV-1. Investigations will also be performed to determine if B5 influences HSV-1 spread, whether it interacts with ligands, and whether it associates with HVEM; 3) to examine if and how B5 interacts with viral and cellular proteins to mediate HSV entry and membrane fusion.