恒河猴感染H5N1禽流感病毒后肺组织病理变化及病毒分布

Distribution of influenza A （H5N1） virus and pathological lesions in major organ tissues of experimentally infected rhesus macaques

目的 探讨恒河猴感染H5N1病毒后肺组织病理变化及病毒分布特点.方法 在麻醉状态下对4只雄性恒河猴经鼻部滴入H5N1禽流感病毒（AF148678/ACGoose/Guangdong/11961H5N1）,在染毒后第1、3、6及14天分别剖杀1只恒河猴.HE染色观察主要组织器官的病理变化,应用实时荧光（RT）-PCR及免疫组织化学方法分析H5N1禽流感病毒侵袭机体后肺及其他主要器官的病理改变及病毒分布情况.结果 恒河猴感染H5N1禽流感病毒后,病毒仅在肺组织复制,主要侵犯肺泡上皮细胞和肺巨噬细胞,表现为弥漫性肺泡损伤,先后经历渗出期、增生期和纤维化期.在肺外主要器官也观察到变性、坏死等病理变化,但均未分离出病毒.结论 H5N1禽流感病毒感染引起的急性弥漫性肺损伤是主要病理改变.肺脏是H5N1禽流感病毒主要攻击对象,下呼吸道以外的组织器官中未见到病毒复制,这可能是H5N1禽流感病毒在人与人之间传递的障碍之一.

Objective To investigate the pathological changes and viral invasion in the main organs of rhesus macaques after experimental infection with H5N1 virus.Methods The rhesus macaques were infected with H5N1 virus （AF148678/ACGoose/Guangdong/11961H5N1） by nasal inoculation under anesthesia.One rhesus macaque was killed respectively at 1,3,6,14 days after infection.The pathologic changes of the main organs were observed using HE staining and the characteristics of the viral invasion in the body were analyzed using viral isolation,RT-PCR andimmunohistochemistry.Results The influenza virus replicated only in the lung tissues characterized by diffuse alveolar damage in the infected rhesus macaques,mainly involving alveolar epithelial cells and pulmonary macrophages.The pathological changes showed 3 phases including exudative inflammation,hyperplasia and fibrosis.Extra-pulmonary organs also showed different degree of pathological changes such as degeneration and necrosis,but virus was not isolated in the corresponding organs.Conclusions Acute diffuse lung injury was a central part of the pathogenesis in H5N1 avian influenza virus infection.The lung was the main target organ in H5N1 viral infection,and H5N1 virus cannot replicate in other organs,which may be one of the obstacles to H5N1 viral transmission from person to person.