CELLULAR IMMUNE RESPONSE IN RESPIRATORY VIRUS INFECTIONS

该计划的总体目标是理解关键 呼吸道病毒免疫在细胞和分子方面的研究 级别，长期目标是开发新的方法来 免疫和治疗。分析集中在副流感上 1型病毒是幼儿的天然病原体(hPIV-1)和 实验室小鼠(仙台病毒)。这两种病毒大约有72% 到目前为止已经测序的基因的同源性，并显示 广泛交叉中和的证据。基本方法是 利用仙台病毒感染小鼠的实验分析 人类hPIV-1不能充分解决的问题。 前5年的重点将是定义 病毒蛋白/多肽与病毒特异性的分子相互作用 免疫球蛋白(Ig)分子(方案1和5)和T细胞(方案2 和3)，以表征促进恢复的细胞机制 急性感染(项目3)，并建立以下参数 在免疫记忆和抵抗二次感染方面发挥重要作用 (方案1和5)和T淋巴细胞(方案2和4)。项目1和 2将集中于hPIV-1，而项目3-5将主要 与仙台病毒有关。该项目汇集了5名调查人员 来自免疫学、病毒学和分子生物学系 圣犹大儿童研究医院。这一组具有概念性和 技术广度带来广泛的当代病毒学和 免疫学方法与宿主反应的一般问题有关 抵抗呼吸道病毒感染。 因此，有关机制的问题源于 人类T细胞记忆的定义和hPIV-1的特异性将是 在携带仙台病毒的小鼠身上进行了分析。关于结构-功能的发现 来自分子和T淋巴细胞的关系和B和T淋巴细胞谱系的使用 体外细胞分析将在体内进行生物学测试 关联性。这种互动所产生的洞察力， 多学科方法将为以下两方面提供坚实的基础 后来开发了新的方法来改善这些疾病过程，以及 专注于将年轻的调查人员介绍给建筑群和 病毒免疫的重要领域。

The overall objective of the program is to understand key aspects of immunity to respiratory viruses at the cellular and molecular levels, with the long-term goal of developing novel approaches to immunization and therapy. The analysis concentrates on parainfluenza type 1 viruses that are natural pathogens of young children (hPIV-1) and laboratory mice (Sendai virus). These two viruses are approximately 72% homologous for the genes that have been sequenced so far, and show evidence of extensive crossneutralization. The basic approach is to utilize Sendai virus infection in the mouse for the experimental analysis of questions that cannot be addressed adequately for hPIV-1 in humans. The emphasis over the first 5 years will be to define the nature of the molecular interactions between viral proteins/peptides and virus specific immunoglobulin (Ig) molecules (Projects 1 and 5) and T cells (Projects 2 and 3), to characterize the cellular mechanisms promoting recovery from acute infection (Project 3), and to establish the parameters that are central to immunological memory and resistance to re-infection for both B (Projects 1 and 5) and T lymphocytes (Projects 2 and 4). Projects 1 and 2 will concentrate on hPIV-1, while Projects 3-5 will be largely concerned with Sendai virus. The program draws together 5 investigators from the Departments of Immunology, and Virology and Molecular Biology at St Jude Children's Research Hospital. This group has the conceptual and technical breadth to bring a broad range of contemporary virology and immunology approaches to bear on the general problem of host response and resistance to respiratory virus infection. Thus, questions concerning mechanisms that arise from the definition of T cell memory and specificity to hPIV-1 in humans will be analyzed in mice with Sendai virus. Findings on structure-function relationships and B and T lymphocyte repertoire usage from molecular and cellular analysis in vitro will be tested in vivo for biological relevance. The insights that are generated by this interactive, multidisciplinary approach will provide both a substantial basis for the later development of new ways to ameliorate these disease processes, and excellent focus for introducing young investigators to the complex and important area of viral immunity.