裸鼠呼吸道合胞病毒感染的动物模型

呼吸道合胞病毒(RSV)是全世界婴幼儿下呼吸道感染的首位病毒病原体,免疫缺陷个体容易发生严重感染,目前尚无理想RSV感染动物模型用于研究。我们用细胞免疫缺陷裸鼠感染RSV,旨在建立理想的动物模型,为RSV感染的防治研究奠定基础。裸鼠滴鼻感染RSV后肺组织分离到病毒,直接免疫荧光检测到支气管肺泡灌洗液RSV抗原阳性,空斑形成实验检测肺组织病毒滴度在感染后第3天达高峰,并持续到第9天仍能检测到病毒。免疫组化检测RSV抗原主要分布在细支气管、毛细支气管和肺泡上皮细胞胞浆内。肺组织病理学显示RSV感染导致裸鼠淋巴细胞浸润为主的肺间质性炎症,电镜分析超微结构可见到细胞内病毒颗粒和气血屏障的破坏。支气管肺泡灌洗液白细胞计数显示裸鼠RSV感染炎症高峰在感染后第9天。裸鼠RSV感染的病毒复制和病理改变特点与人相似,病毒持续高水平复制,是客观而实用的评价抗RSV制剂效果的小鼠模型。

Animal Model of Respiratory Syncytial Virus Infection in Nude Mice

Respiratory syncytial virus ( RSV) is a worldwide leading viral cause of lower respiratory tract infection in children. Immunodeficient individuals are vulnerable to severe RSV infection. No ideal animal model is available at the present time. To establish an ideal murine model, RSV was dripped in tranasally into cellular immunodeficient nude mice, then pulmonary virus was isolated and viral antigen in bronchi-alveolar lavage fluid was identified by direct immunofluorescent assay. Pulmonary viral titers detected by plaque forming assay, peaked on the 3rd day post infection, and were still detectable by the 9th day post infection. RSV antigen was mainly localized in cytoplasm of alveolus and bronchioles by immunohistochemistry assay. RSV infected nude mice developed interstitial pneumonia with prominent lymphocyte infiltration; meanwhile the virus destroyed the air-blood barrier and viral inclusions were found by electron microscopy. The numbers of leukocyte in bronchi-alveolar lavage fluid increased significantly and peaked at the 9th day post infection. All these results indicated that RSV infected nude mice showed similar patterns of viral replication and pulmonary histopathology as with infected humans, and had a high level, durative viral replication. Therefore, RSV infected nude mice appears to be a workable murine model for assessing the effect of antiviral agents against RSV.