A New Animal Model for Human Respiratory Tract Disease Due to Adenovirus

Cotton rats (Sigmodon hispidus) were tested as a model for human respiratory tract infection due to adenovirus. After intranasal instillation of 106.1 50% tissue culture infectious doses (TCID50) of adenovirus type 5 into one-month-old cotton rats, groups were killed at intervals for nasal and lung titration of virus and lung histopathology. In lung, eclipse occurred at 8 hr followed by peak viral titer (107.5 TCID50/g of lung) on day 5. Titers fell to 103.2 TCID50/g by day 10 and persisted at that level through the remainder of the study (day 28) despite appearance of serum neutralizing antibody after day 6. Interstitial pneumonia paralleled viral growth, and peribronchial mononuclear infiltration followed one to two days later. Titers in nasal mucosa peaked on day 3 but were undetectable beyond day 21. Pulmonary histopathology and viral replicative patterns paralleled findings in natural human disease.