VIRAL AND CELL DETERMINANTS OF HSV DISEASE

HSV 疾病的病毒和细胞决定因素

• 批准号: 6201127
• 负责人: PATRICIA G SPEAR
• 金额: $ 13.74万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6201127
• 关键词: cooperative study; epithelium; female; gene mutation; herpes simplex virus 1; herpes simplex virus 2; host organism interaction; laboratory mouse; molecular pathology; nervous system infection; sexually transmitted diseases; tissue /cell culture; vagina; virus infection mechanism; virus receptors; virus replication

The ultimate objective of studies described here is to define viral and cell requirements for the entry of herpes simplex viruses types 1 and 2 (HSV- 1 and HSV-2) into cells of the genital tract and for spread of infection from the portal of entry to other tissues, particularly the nervous system. Mice inoculated via the vaginal route will provide an animal model of disease. This mouse model of infection and disease is likely to provide information relevant to human disease in part because human and mouse cell receptors for viral entry are homologues (encoded by evolutionarily related genes) and because many aspects of sexually transmitted disease caused by HSV in humans are similar to those observed in mice into inoculated via the vaginal route. Recently we cloned three different cDNAs encoding mouse receptors capable of mediating HSV entry into cells. All are homologous to known human receptors for HSV entry. We have also identified viral mutations that influence receptor usage or viral spread within the vaginal epithelium. The specific aims are to: 1) Determine whether the three mouse receptors cloned to date can account for the susceptibility of various cultured mouse cell types to HSV-1 and HSV-2 entry. 2) Identify viral mutations that alter receptor usage by HSV-1 and HSV-2. 3) Determine which mouse receptors are used by HSV-1 and HSV-2for entry into cells of the vaginal epithelium and for spread to other cell types including leukocytes and cells of the nervous system. The results of these studies will define molecular identify new approaches to protection of the vaginal epithelium and/for the nervous system from infection. In addition, they may identify strategies for the development of safer non-neurotropic vaccine strains of HSV.

此处描述的研究的最终目标是将单纯疱疹病毒类型1和2（HSV-1和HSV-2）的进入的病毒和细胞需求定义为生殖道细胞的细胞，以及从进入其他组织的门户，尤其是神经系统的入口处传播感染。通过阴道途径接种的小鼠将提供疾病的动物模型。这种感染和疾病的小鼠模型可能会提供与人类疾病相关的信息，部分原因是人类和小鼠细胞受体的病毒输入受体是同源物（由进化相关的基因编码），并且因为人类引起的性传播疾病的许多方面与通过阴道途径在小鼠中被发现的小鼠相似。最近，我们克隆了三个不同的cDNA，编码能够介导HSV进入细胞的小鼠受体。所有这些都与已知的HSV进入的人类受体同源。我们还确定了影响受体使用或阴道上皮内病毒传播的病毒突变。具体目的是：1）确定迄今为止克隆的三个小鼠受体是否可以解释各种培养的小鼠细胞类型对HSV-1和HSV-2进入的敏感性。 2）确定因HSV-1和HSV-2改变受体使用的病毒突变。 3）确定HSV-1和HSV-2用于进入阴道上皮细胞的细胞，并扩散到其他细胞类型，包括白细胞和神经系统细胞，用于传播。这些研究的结果将定义分子确定保护阴道上皮和/神经系统免受感染的新方法。此外，他们可以确定开发HSV的更安全的非神经疫苗疫苗菌株的策略。