Reactivation of persistent papovavirus K infection in immunosuppressed mice

Papovavirus K (K virus) is a murine papovavirus that produces a fatal interstitial pneumonia in newborn mice and a clinically inapparent infection in older animals. The present study was conducted to determine whether the virus produces latent infection in animals surviving acute infection and whether the infection can be reactivated by immunosuppression. Mice were inoculated by the oral route with 100 newborn mouse 50% lethal doses at 12 days of age and followed for 8 months by using immunofluorescence staining. Cells positive for K virus capsid antigen were found in lungs, livers, kidneys, intestines, and brains for 6 months, but not thereafter. Organ examined at 8 months were negative for virus by tissue culture assay, mouse inoculation, explantation, and cocultivation. Immunosuppression of the remaining animals with 8 weekly injections of cyclophosphamide (150 mg/kg) resulted in the reappearance of viral antigen and infectious virus in multiple organs including brains. The highest titers of virus were present in kidneys. One animal sacrificed after 42 days of immunosuppression was found to have a small pulmonary adenoma or alveologenic carcinoma, but efforts to explant this tumor into tissue culture were unsuccessful. The present study demonstrates that K virus produces a latent infection that is reactivated by immunosuppression, and our results raise questions as to whether reactivated infection may occasionally be associated with the development of neoplasia.