EFFECTORS OF IMMUNE PROTECTION FROM HSV LATENCY

HSV 潜伏期免疫保护的影响因素

• 批准号: 2796208
• 负责人: MARTHA F KRAMER
• 金额: $ 3.67万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-10-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2796208
• 关键词: Alphaherpesvirinae; active immunization; immunocytochemistry; in situ hybridization; laboratory mouse; latent virus infection; microorganism immunology; polymerase chain reaction

The objectives of this proposal are to define immune effectors of protection from HSV latency induced by vaccination with a replication-defective HSV mutant virus. The specific aims are to quantify latency following challenge in immune and non-immune mice depleted and non-depleted or reconstituted with antibody, immune cell subtypes, and selected cytokines at the time of challenge. This focuses on an important puzzle in HSV pathology, namely how latency is established, maintained, and reactivated in the presence of a specific, vigorous, anamnestic immune response. Reactivation can have dire consequences. Stromal keratitis, a leading cause of blindness is considered an auto-immune disease and is associated with recurrent, not primary, HSV infection. The proposed research is designed to elucidate immune components involved in establishment and maintenance of latency and implicated in escape from latency and consequent initiation of disease, and to provide a model for testing vaccine and therapeutic strategies. The research design will be to vaccinate mice with replication-defective HSV and, following challenge with a virulent strain of HSV, to quantify latency in ganglia, the site of latent infection. Immune effectors of protection will be define using complement-mediated depletion, adoptive transfer, and immunohistochemistry. Latency will be quantified by in situ hybridization of the abundant latent viral RNA, LAT, and by in situ PCR.

该提案的目标是定义 防止因疫苗接种而引起的HSV潜伏期 复制缺陷性HSV突变病毒。 具体目的是 在免疫和非免疫小鼠的挑战后量化潜伏期 用抗体，免疫细胞耗尽，无耗电或重组 亚型和挑战时选择的细胞因子。 这是集中的 在HSV病理学的重要难题中，即潜伏期 在特定的存在下建立，维护和重新激活 剧烈的吞噬免疫反应。 重新激活可能会有可怕的 结果。 基质角膜炎，失明的主要原因是 被认为是一种自身免疫性疾病，与经常性有关， 不是主要的HSV感染。拟议的研究旨在 阐明参与建立和 维持潜伏期，并涉及逃避潜伏期和 随之而来的疾病开始，并提供测试模型 疫苗和治疗策略。 研究设计将是 用复制缺陷的HSV疫苗接种小鼠，然后 用强烈的HSV菌株挑战，以量化神经节潜伏期， 潜在感染部位。保护的免疫效应因素将是 使用补体介导的耗竭，收养转移和 免疫组织化学。 延迟将通过原位量化 丰富的潜在病毒RNA，LAT和原位的杂交 pcr。