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Cultures of human rhabdomyosarcoma (RD) and human glioblastoma (U87-MG) were compared for their ability to sustain a persistent infection with coronavirus OC43. Within 28 days, infectious virus and hemagglutinin were being produced at high levels in both types of cells. Temperature sensitive plaque variants were recovered at 31 degrees C. In both cell types, the virus caused increased antigen synthesis and cell death, if the temperature was lowered to 31 degrees C. Infectious virus was lost if cells were treated with antiserum to whole virus or if the temperature was raised to 39.5 degrees C. Probing the cured cells with OC43-specific 32P-cDNA showed that cured cells contained no detectable viral RNA. The relative ease of establishment and cure of these persistent infectious makes them attractive as models to study coronavirus regulatory processes.