GENETIC DETERMINANTS MEDIATING VIRUS INDUCED LUNG INJURY

呼吸道合胞病毒(RSV)是全世界幼儿毛细支气管炎和肺炎的最常见原因。S在20世纪60年代研制的一种实验性呼吸道合胞病毒疫苗，在随后自然感染呼吸道合胞病毒后，会导致婴儿病情加重。最近使用近交系小鼠的研究表明，CD4T细胞以及其他未知的遗传因素，在实验性RSV感染期间对RSV疫苗增强的肺部病理起到了促进作用。这项建议概述了一种双管齐下的方法，旨在(1)在实验性RSV感染的小鼠模型中表征RSV特异性记忆CD4T细胞对肺部感染的反应，以及(2)识别导致RSV疫苗增强型肺损伤的宿主遗传因素。这些分析结果将有助于我们理解介导RSV疫苗增强型肺部疾病的细胞和遗传因素，并为开发安全有效的RSV疫苗提供必要的有价值的信息。

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.