Vitalis T Z, Keicho N, Itabashi S, Hayashi S, Hogg J C
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Am J Respir Cell Mol Biol. 1996 Mar;14(3):225-31. doi: 10.1165/ajrcmb.14.3.8845172.
A model of adenovirus 5 (Ad5) infection was developed in guinea pigs to begin to study its role in the pathogenesis of peripheral lung inflammation. Forty animals were inoculated intranasally with 10(7.0) pfu of Ad5/animal, and 15 animals inoculated with sterile culture media served as controls. Viral titres were 10(4.4), 10(6.1), 10(5.2), and 10(2.9) pfu/animal, on days 1, 3, 4, and 7 after infection, respectively. In situ hybridization to viral DNA and immunocytochemistry for Ad5 E1A protein localized the virus to airway and alveolar epithelial cells. Histologic examination showed an extensive inflammatory cell infiltration around the airways, with epithelial necrosis and an alveolar exudate that caused localized alveolar collapse in the infected areas. Immunocytochemistry identified the cells in the infiltrate as cytotoxic T cells. Although all animals 20 and 47 days after infection had seroconverted to Ad5, virus was not detected in these groups either by viral plaque assay or in situ hybridization. Ad5 E1A DNA was detected by polymerase chain reaction in five of six animals 20 days after infection and in five of five animals 47 days after infection. In these same animals, E1A protein was detected 20 days after infection in two and 47 days after infection in one while persistent bronchiolitis was observed in four and three animals 20 and 47 days after infection, respectively. These results demonstrate that the guinea pig provides a useful model to study the role of Ad5 infection in chronic airway inflammation.
为了开始研究腺病毒5型（Ad5）在周围性肺部炎症发病机制中的作用，在豚鼠中建立了Ad5感染模型。40只动物经鼻接种10(7.0) 个空斑形成单位（pfu）/只的Ad5，15只接种无菌培养基的动物作为对照。感染后第1、3、4和7天，病毒滴度分别为10(4.4)、10(6.1)、10(5.2) 和10(2.9) pfu/只。对病毒DNA进行原位杂交以及对Ad5 E1A蛋白进行免疫细胞化学检测，将病毒定位到气道和肺泡上皮细胞。组织学检查显示气道周围有广泛的炎性细胞浸润，伴有上皮坏死和肺泡渗出物，导致感染区域局部肺泡萎陷。免疫细胞化学鉴定浸润细胞为细胞毒性T细胞。尽管感染后20天和47天所有动物均已对Ad5血清转化，但在这些组中通过病毒蚀斑试验或原位杂交均未检测到病毒。感染后20天，6只动物中有5只通过聚合酶链反应检测到Ad5 E1A DNA，感染后47天，5只动物中有5只检测到。在这些相同的动物中，感染后20天有2只检测到E1A蛋白，感染后47天有1只检测到，而感染后20天和47天分别有4只和3只动物观察到持续性细支气管炎。这些结果表明豚鼠为研究Ad5感染在慢性气道炎症中的作用提供了一个有用的模型。
