INFECTION with respiratory viruses usually results in a mild transitory disease from which the host recovers. Our experience with Sendai-virus infection of the mouse suggests that the lack of severity of these infections is due to the induction of powerful defence mechanisms Heath, 1968 and1969;Blandford, Cureton and Heath, 1971). To obtain further information on these mechanisms, a virulent variant of a normally harmless influenza virus was obtained by serial passage in the lungs of mice. A comparative study was then made of the pathogenesis of the infections caused by this variant and the original avirulent virus.MATERIALS AND METHODS Virus. The Kunz strain of influenza-A virus was used, and was propagated in the allantoic cavity of 10-day-old embryonated hens' eggs. Dilutions of virus were prepared in broth saline for inoculation into mice and in medium 199 for inoculation into monkey kidney tissue cultures.Infection of mice. Five-week-old CD1 mice were lightly anaesthetised and were infected by the intranasal inoculation of 0-1-ml volumes of virus suspensions. At various intervals after this, groups of six mice were weighed and were then exsanguinated under ether anaesthesia. Their lungs were removed, examined, weighed and then processed for histology or for determination of virus and interferon titres. The blood samples taken at these times were retained for assay of serum antibodies by HI. Lung lesions were scored by the method of Horsfall (1939).Mouse-infectivity titres (MIDSO) were determined by inoculating serial 10-fold dilutions of virus into batches of ten mice. Deaths associated with typical pneumonitis and the presence of specific antibodies in the serum of mice surviving to the 14th day after inoculation were taken as evidence of infection. Titres were calculated by the method of Reed and Muench (1 938).Details of the histological and other assay procedures used have been given in previous papers (Robinson et al., 1968;Blandford et al., 1971 ;Blandford and Heath, 1972).Immzmojluorescence. Viral antigens and immunoglobulin-containing cells were detected by means of an indirect immunofluorescence technique as previously described (Blandford et al., 1971;Heath, 1972 and1974). A rabbit antiserum against Kunz virus was used for detecting viral antigens, and a rabbit anti-mouse-immunoglobulin serum for immunoglobulin-containing cells.

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SUMMARYThe antiviral responses in mice to intranasal inoculation with Sendai virus are described. To investigate the relative importance of the humoral, cell-mediated and interferon responses, the pathogenesis of this infection was studied in animals which were immunocompetent, T cell-deprived or immunosuppressed with cyclophosphamide. Treatment with cyclopbosphamide converted the mild, self-limiting infection observed in immunocompetent mice into a severe and frequently lethal pneumonic disease. This was associated with an enhanced interferon response but no detectable antibody or cell-mediated immune response. T cell-deprived mice suffer an infection of intermediate severity associated with an increased interferon response, a normal humoral immune response and no cell-mediated immune response. The implications of these results in relation to the role of the antiviral responses in recovery from Sendai virus infection are discussed.