Pulmonary lesions in primary respiratory syncytial virus infection, reinfection, and vaccine-enhanced disease in the cotton rat (Sigmodon hispidus).

Infection of the cotton rat lung with a human strain of respiratory syncytial virus results in substantial virus replication and is associated with mild-to-moderate peribronchiolitis, perivasculitis, and bronchitis. Reinfection after 49 days did not result in detectable virus replication, but surprisingly, was associated with an earlier appearance and accentuation of the three types of lesions seen in cotton rats undergoing primary infection. Animals primed with formalin-inactivated virus and challenged after 49 days had pulmonary viral titers 1/10 to 1/100 of that seen in naive animals, but developed markedly accentuated lesions of the same type as in animals undergoing primary or secondary infection. In addition, the animals with the vaccine-enhanced disease developed alveolitis and interstitial pneumonitis, which seem to be specific markers for the vaccine enhancement. These latter markers may be useful in determining the safety of nonreplicating vaccines.