Rabies serogroup viruses in neuroblastoma cells: propagation, "autointerference," and apparently random back-mutation of attenuated viruses to the virulent state

Abstract

Each of several strains of fixed rabies virus replicated to high titers in C1300 mouse neuroblastoma (clone NA) cells without adaptation. Rabies serogroup Lagos bat, Mokola and Duvenhage viruses replicated efficiently in NA cells. Kotonkan and Obodhiang viruses replicated efficiently after adaptation to titers not previously obtained in vitro. Infection in NA cells was frequently more cytopathic than in BHK-21 cells, allowing titration of Kotonkan and Obodhiang viruses by plaque assay. Duvenhage virus caused syncytium formation. Serial propagation of rabies viruses at a high multiplicity of infection in NA cells led to a rapid decline in virus yields; similar autointerference was not demonstrated with rabies virus in other cell systems. Rabies virus infection in NA cells exhibited extreme sensitivity to interference by experimentally added defective interfering virions. Although several strains of attenuated rabies virus consistently reverted rapidly to virulence after propagation in NA cells, other strains of attenuated rabies and rabies serogroup viruses acquired increased virulence at a more gradual rate or not at all. Diverse characters may control virulence. When attenuated Flury HEP rabies virus was serially propagated at a low multiplicity of infection in NA cells or suckling mouse brain, virulence appeared at a very variable rate. These systems may selectively enhance replication of randomly occurring virulent virus mutants.