Evaluation of severe disease induced by aerosol inoculation of calves withbovine respiratory syncytial virus

Objective-To develop a model of bovine respiratory syncytial virus (BRSV) i nfection that induces severe disease similar to that seen in some cattle wi th naturally acquired BRSV infection. Animals-25 male Holstein calves, 8 to 16 weeks old. Procedure-17 calves were given a low-passage field isolate of BRSV by aeros olization; 8 control calves were given supernatant from noninfected cell cu lture. Disease was characterized by evaluating clinical signs, virus isolat ion and pulmonary function tests, and results of blood gas analysis, gross and histologic postmortem examination, and microbiologic testing. Results-Cumulative incidence of cough, harsh lung sounds, adventitious soun ds, and dyspnea and increases in rectal temperature and respiratory rate we re significantly greater in infected calves. Three infected calves develope d extreme respiratory distress and were euthanatized 7 days after inoculati on. Virus was isolated from nasal swab specimens from all infected calves b ut not from mock infected calves. On day 7 after inoculation, mean PaO2 and PaCO2 were significantly lower, and pulmonary resistance was significantly higher, in infected calves. During necropsy, infected calves had varying d egrees of necrotizing and proliferative bronchiolitis and alveolitis with s yncytial formation. The 3 calves euthanatized on day 7 had emphysematous bu tlae in the caudal lung lobes; 1 had unilateral pneumothorax. Conclusion and Clinical Relevance Severe disease similar to that seen in so me cattle with naturally acquired BRSV infection can be induced in calves w ith a single aerosol exposure of a low-passage clinical isolate of BRSV. Ou r model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.