CELLULAR RECEPTORS FOR HERPES SIMPLEX VIRUS

单纯疱疹病毒(HSV)是进入人类的一种主要病原体 通过与pH无关的病毒-细胞级联反应的敏感细胞 互动。虽然许多研究都集中在了解细胞因子的功能 病毒成分，最近的发展使细胞研究成为可能 有助于HSV进入的组件。所涉及的蜂窝组件 病毒最初附着的是硫酸乙酰肝素(HS)。组件(S) 负责稳定的附着，无论是HS还是推定的蛋白质 受体，仍有待鉴定。这项提议的目标是 稳定依恋受体的分离、鉴定和鉴定(S) HSV-1在传染性入境期间使用的。研究设计充分利用了 最近的识别和表征提供了独特的机会 由于进入缺陷而不容易感染HSV的细胞。 具体目标是：(1)将易感性从 敏感的人类细胞对低敏感或不敏感的细胞克隆 编码单纯疱疹病毒稳定附着受体的基因(S)，(2)证实 并从病毒细胞印迹中鉴定出一种110kd的蛋白质为生化 一种分离和鉴定蛋白质(S)的方法 和(3)使用AIMS 1和AIMS生产的试剂 2产生抗受体抗体以鉴定受体和 它在HSV进入和趋向性中的作用。这些不同，但互补的， 方法应与总体目标协同增效。他们是 可行是因为电池的可用性缺乏功能上的非 单纯疱疹病毒进入时需要肝素样受体。确定一个马厩 HSV-1的附着受体对a的长期目标很重要) 了解病毒如何穿过细胞膜启动基因 在自然感染过程中的表达，b)使用疱疹病毒作为载体， C)制定规避单纯疱疹病毒和其他病毒感染的策略 导致发病和死亡的主要人类病毒病原体，以及d) 确定融合和通信的分子机制 生物膜。

Herpes simplex virus (HSV) is a major human pathogen that enters susceptible cells through a pH independent cascade of virus-cell interactions. While many studies focus on understanding the function of viral components, recent development allow investigation of the cellular components that contribute to HSV entry. The cellular component involved in initial attachment of virus is heparan sulfate (HS). The component(s) responsible for stable attachment, whether HS or a putative protein receptor, remains to be identified. The objective of this proposal is to isolate, identify and characterize the stable attachment receptor(s) used by HSV-1 during infectious entry. The research design exploits the unique opportunity provided by recent identification and characterization of cells that are poorly susceptible to HSV due to a defect in entry. The specific aims are (1) to transfer susceptibility from highly susceptible human cells to low or not susceptible cells to clone the gene(s) encoding the HSV stable attachment receptor(s), (2) to confirm and characterize a 110 kd protein from virus-cell blots as a biochemical approach to isolate and identify the protein(s) which serve as the receptor on human cells, and (3) to use reagents produced in Aims 1 and 2 to generate anti-receptor antibodies to characterize the receptor and its role in HSV entry and tropism. These different, but complementary, approaches should be synergistic to the overall objective. They are feasible because of availability of cells that lack a functional non- heparin-like receptor required in HSV entry. Identifying a stable attachment receptor for HSV-1 is important to long-term goals of a) understanding how viruses cross the cell membrane to initiate gene expression during natural infection, b) using herpesviruses as vectors, c) designing strategies for circumventing infection of HSV and other major human virus pathogens which cause morbidity and mortality, and d) determining molecular mechanisms for fusion and communication across biological membranes.