VIROLOGIC AND IMMUNOLOGIC STUDIES OF MURINE CMV RETINITI

描述：(改编自申请人的摘要)申请人有 最近证实，将MCMV接种到眉骨上间隙 免疫活性BALB/c小鼠的视网膜病变 免疫功能低下的人眼内观察到相同的组织病理学特征 巨细胞病毒视网膜炎患者。拟议中的第一个实验将是 在具有免疫功能的BALB/c小鼠身上进行。调查员将使用 病毒学、免疫学和分子生物学技术来确定 接种病毒后病毒复制的程度和位置 进入眉上间隙，病毒潜伏部位，以及全身 免疫反应。在这些实验之后，将执行 选择病毒剂量的剂量反应实验，以产生最小的 最初感染时视网膜受累，但会导致 视网膜(和/或其他眼部结构)的潜伏期。申请人 然后建议使用各种特异性(耗尽T细胞亚群)和 非特异性免疫抑制策略以重新激活病毒和 产生视网膜炎。

DESCRIPTION: (Adapted from applicant's abstract) The applicant has recently demonstrated that inoculation of MCMV into the supraciliary space of immunocompetent BALB/c mice results in a retinitis that has some of the same histopathologic features observed in eyes of immunocompromised human patients with CMV retinitis. The first of the proposed experiments will be performed in immunocompetent BALB/c mice. The investigator will use virologic, immunologic and molecular biological techniques to determine the extent and location of virus replication following inoculation of virus into the supraciliary space, sites of viral latency, and the systemic immune response. These experiments will be followed by performance of dose-response experiments to select a dose of virus that results in minimal retinal involvement at the time of initial infection but which produces latency in the retina (and/or in other ocular structures). The applicant then proposes to use various specific (depletion of T cell subsets) and non-specific strategies of immunosuppression to reactivate virus and produce retinitis.