The generation of small-plaque mutants during undiluted passage of canine distemper virus

A culture of Vero cells persistently infected with undiluted-passage, large-plaque canine distemper virus was found to release small-plaque virus (SPV). This suggested that SPV could be generated by large-plaque virus (LPV). However, attempts to induce small-plaque mutants from LPV with 5-fluorouracil resulted in the production of virus that expressed a variable plaque type and induced a spectrum of disease in hamsters. In contrast, small-plaque mutants, shown to arise during undiluted passage of LPV, retained their small-plaque characteristic and resembled our original SPV isolate in their cytopathogenicity, immunogenicity, and neurovirulence for hamsters.