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

Objective - To develop a model of bovine respiratory syncytial virus (BRSV) infection that induces severe disease similar to that seen in some cattle with naturally acquired BRSV infection. Animals - 25 male Holstein calves, 8 to16 weeks old. Procedure - 17 calves were given a low-passage field isolate of BRSV by aerosolization; 8 control calves were given supernatant from noninfected cell culture. Disease was characterized by evaluating clinical signs, virus isolation 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 sounds, and dyspnea and increases in rectal temperature and respiratory rate were significantly greater in infected calves. Three infected calves developed extreme respiratory distress and were euthanatized 7 days after inoculation. Virus was isolated from nasal swab specimens from all infected calves but 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 degrees of necrotizing and proliferate bronchiolitis and alveolitis with syncytial formation. The 3 calves euthanatized on day 7 had emphysematous bullae in the caudal lung lobes; 1 had unilateral pneumothorax. Conclusion and Clinical Relevance - Severe disease similar to that seen in some cattle with naturally acquired BRSV infection can be induced in calves with a single aerosol exposure of a low-passage clinical isolate of BRSV. Our model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.