Potential small animal models for virus-induced chronic respiratory disease.

Although several clinical studies have suggested that some of the acute exacerbations of chronic bronchitis may be produced by certain viruses, the precise role of these agents in the pathogenesis of progressive chronic respiratory disease has not yet been defined.`8 The prolonged and complex natural history of chronic respiratory disease in man has made it extremely difficult to assess the role of viruses in this disease by classical epidemiologic methods. The development of a model system for the viral induction of chronic respiratory disease in the small laboratory animal might eliminate some of these problems and would provide an experimental basis for assessing the possible role of viral infection in the initiation and progression of chronic respiratory disease in man. Since many of the human respiratory viruses such as the adenoviruses, parainfluenza viruses, respiratory syncytial virus and the rhinoviruses produce either an inapparent infection or no infection at all in small laboratory animals, these animals have not been very useful in studies of the pathogenesis of viral respiratory infections caused by these agents.`7 Influenza virus, however, will produce an acute upper respiratory infection in the unanesthetized ferret. If the ferrets are given ether at the time of inoculation, the disease produced will become more severe with serial passage.8 The virus will then become adapted to the lungs and produce an extensive pneumonia which is often fatal. In addition, influenza virus can be adapted to produce a lethal pulmonary disease in mice.8' To date, experimental infection of small laboratory animals with these viruses has not been shown to induce chronic respiratory disease. This accumulated experience suggests that, with the possible exception of the influenza viruses, it is unlikely that the direct inoculation of small laboratory animals with human respiratory viruses will produce a suitable laboratory model of viral chronic respiratory disease. A systematic study of indigenous animal viruses as possible causes of chronic respiratory disease in small laboratory animals has not been undertaken. There are many animal viruses that belong to the same virus groups as the human respiratory viruses and the use of these viruses for the induction of experimental viral chronic respiratory disease might overcome the