VIRAL PERSISTENCE: GENETIC AND IMMUNOLOGICAL STUDIES

这些研究的长期目标是了解 病毒逃避或抑制免疫的机制 响应并在宿主中持续存在。 病毒的机制 持久性仍然是病毒学中未解决的主要问题。 虽然报告的几种急性病毒感染的发病率 近年来，持续性病毒感染的发病率有所下降， 感染一直在增加。 这是最戏剧性的 获得性免疫缺陷综合征（艾滋病）就是例证。 慢性B型肝炎病毒感染也稳步增加 目前估计有超过两亿的病毒携带者。 在 此外，持续的病毒感染与 某些肿瘤和免疫病理学疾病。 淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染小鼠 提供了一个很好的模型来研究 病毒和它的自然宿主的免疫系统， 定义导致病毒清除或持续存在的条件。 拟议研究的目标有两个方面。 一是 分析野生型LCMV和 LCMV变体，并确定LCMV的精确位置。 这些突变使这些变异体能够抑制病毒特异性T细胞 细胞反应并导致成年小鼠的持续感染。 第二，检查变体与T细胞的相互作用， 和巨噬细胞来阐明 免疫抑制 这些研究结合了 病毒学和免疫学，应该导致一个改进的基本 了解慢性病毒感染的发病机制

The long-term goal of these studies is to understand the mechanisms by which viruses evade or suppress the immune response and persist in the host. The mechanism of viral persistence remains a major unresolved problem in virology. While the reported incidence of several acute viral infections has declined in recent years, the incidence of persistent viral infections has been increasing. This is most dramatically illustrated by the acquired immune deficiency syndrome (AIDS). Chronic hepatitis B virus infections have also steadily increased with current estimates of over 200 million virus carriers. In addition, persistent viral infections have been associated with certain 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 two-fold. First, to analyze the genetic differences between wild type LCMV and LCMV variants and to identify the precise location of the mutations that allow these varients to suppress virus specific T cell responses and cause persistent infections in adult mice. Second, to examine the interaction of the variants with T cells and macrophages to elucidate the mechanism of immunosuppression. These studies, combining the disciplines of virology and immunology, should lead to an improved fundamental understanding of the pathogenesis of chronic viral infections