VIRAL PERSISTENCE: GENETIC AND IMMUNOLOGICAL STUDIES

病毒持续存在的机制仍然是一个重大的悬而未决的问题 病毒学。这些研究的长期目标是理解 病毒逃避或抑制免疫反应并持续存在的机制 在宿主中。持续的病毒感染具有重大的医学意义，因为 它们通常会对免疫抑制的个体产生严重的后果，而且 也与肿瘤和免疫病理疾病有关。 小鼠感染淋巴细胞性脉络膜脑膜炎病毒(LCMV)可提供 一种研究病毒与病毒相互作用的极佳模型 它的自然宿主的免疫系统，并在定义导致 病毒清除或持续。拟议研究的目标 是三重的。首先，分析野生动物之间的遗传差异 键入LCMV和LCMV变种，并绘制允许 抑制细胞毒性T细胞(CTL)反应并导致持续性的变体 成年免疫能力强的小鼠的感染。第二，确定角色定位 独特器官特异性病毒选择中的宿主器官和细胞类型 变种。第三，检测变异体与T细胞的相互作用 和巨噬细胞，以阐明CTL抑制的机制。这些 结合病毒学和免疫学学科的研究应该 洞察病毒持续存在的遗传基础。

The mechanism of viral persistence remains a major unresolved problem in virology. The long-term goal of these studies is to understand the mechanisms by which virus evade or suppress the immune response and persist in the host. Persistent viral infections are medically significant because they often have severe consequences in immunosuppressed individuals, and have also been associated with neoplasms and immunopathological diseases. Infection of mice with lymphocytic choriomeningitis virus (LCMV) provides an excellent model for studying the interaction between the virus and the immune system of it's natural host, and in defining conditions that lead to viral clearance or persistence. The objectives of the proposed research are three-fold. First, to analyze the genetic differences between wild type LCMV and LCMV variants, and to map the viral genes that allow the variants to suppress cytotoxic T cell (CTL) responses and cause persistent infections in adult immunocompetent mice. Second, to determine the role of host organs and cell types in selection of unique organ specific virus variants. Third, to examine the interaction of the variants with T cells and macrophages to elucidate the mechanism of CTL suppression. These studies, combining the disciplines of virology and immunology, should provide insight into the genetic basis of viral persistence.