GENETIC DETERMINANTS MEDIATING VIRUS INDUCED LUNG INJURY

呼吸道合胞病毒（RSV）是全球幼儿细支气管炎和肺炎的最常见原因。在20世纪60年代开发的实验性RSV疫苗在随后的RSV自然感染后引起婴儿疾病恶化。最近使用近交系小鼠的研究表明，在实验性RSV感染期间，CD4 T细胞以及其他未确定的遗传因子促成RSV疫苗增强的肺病理学。该提案概述了一种双管齐下的方法，旨在（1）表征实验性RSV感染小鼠模型中RSV特异性记忆CD4 T细胞对肺部感染的应答，以及（2）鉴定导致RSV疫苗增强肺损伤的宿主遗传因素。这些分析的结果将有助于我们了解介导RSV疫苗增强的肺部疾病的细胞和遗传因素，并为开发安全有效的RSV疫苗提供有价值的信息。

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia in young children worldwide. An experimental RSV vaccine developed in the 1960's caused exacerbated disease in infants upon a subsequent natural infection with RSV. Recent studies using inbred mice have suggested that CD4 T cells, as well as other undefined genetic factors, contribute to RSV vaccine- enhanced.lung pathology during experimental RSV infections. This proposal outlines a two-pronged approach designed (1) to characterize the RSV-specific memory CD4 T cell response to pulmonary infection in a murine model of experimental RSV infection and (2) to identify host genetic factors that contribute to RSV vaccine- enhanced pulmonary injury. The results of these analyses will aid in our understanding of the cellular and genetic factors that mediate RSV vaccine-enhanced lung disease and provide valuable information necessary for the development of a safe and effective RSV vaccine.