The potential oncogenic activity of influenza A virus in lungs of mice.

Adult male CD1 mice were inoculated with chicken egg-propagated influenza type A/PR8/34 virus. Fully developed pulmonary pneumonia was found 7 d after the infection. In addition to the pneumatic condition, pronounced thickening of the bronchiolar epithelium denoting hyperplastic and dysplastic transformation of the epithelial cells were also observed. By 11 d of the experiment, extensive papillomatous proliferation of the bronchiolar epithelial cells could be demonstrated. Furthermore, invasive growth of these epithelial cells through the basement membrane and muscularis layer into the alveolar tissues were evident. Such invasive transgression of transformed epithelial cells strongly suggested malignant growth of these cells. Detailed histopathological survey of all the virus-infected lungs revealed tumorous nodule formations in over 80% of the specimens examined. Our present investigation not only confirmed previous claims that cellular transformations (hyperplasia, metaplasia, dysplasia) can be induced with influenza type A virus but also for the first time successfully demonstrated invasive growth and tumorous formation in lungs of infected animals. Our study further reaffirms the oncogenic potential of influenza type A virus.