CELLULAR IMMUNE RESPONSE IN RESPIRATORY VIRUS INFECTIONS

该计划的总体目标是了解关键 呼吸道病毒免疫的细胞和分子方面 长期目标是开发新的方法， 免疫和治疗。 分析集中在副流感 1型病毒是幼儿的天然病原体（hPIV-1）， 实验室小鼠（仙台病毒）。 这两种病毒大约占72% 与目前已测序的基因同源，并显示 大量交叉中和的证据 基本方法是 利用仙台病毒感染小鼠进行实验分析 这些问题对于人类中的hPIV-1无法充分解决。 前五年的重点是确定 病毒蛋白/肽与病毒特异性 免疫球蛋白（IG）分子（项目1和5）和T细胞（项目2 和3），表征促进从 急性感染（项目3），并建立参数 对免疫记忆和对B和B细胞再感染的抵抗力起着重要作用 （项目1和5）和T淋巴细胞（项目2和4）。 项目1和 2将集中在hPIV-1，而项目3-5将主要是 关于仙台病毒 该计划吸引了5名调查人员 来自免疫学、病毒学和分子生物学系， 圣裘德儿童研究医院 该小组具有概念性和 技术广度带来了广泛的当代病毒学和 免疫学方法对宿主反应的一般问题产生影响， 抗呼吸道病毒感染。 因此，关于从《公约》产生的机制的问题， T细胞记忆的定义和对人类hPIV-1的特异性将是 用仙台病毒对小鼠进行了分析。 结构-功能研究结果 关系和B和T淋巴细胞库的使用， 体外细胞分析将在体内进行生物学试验 本案无关 这种互动产生的见解， 多学科方法将为 后来开发新的方法来改善这些疾病过程， 优秀的重点介绍年轻的调查人员复杂， 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.