Effects of antibodies and interferon on mumps virus persistently infected L929 cells. Generation of variant viruses in the cells during incubation with monoclonal antibodies and interferon.

We studied the effect of antibodies and interferon (IFN) on L929 cells persistently infected with mumps virus (MuV). The persistent infection was maintained by horizontal transmission of the virus within the culture but was regulated by endogenously produced IFN (8). The maintenance of the persistently infected cells in the continuous presence of anti-MuV serum suppressed the production of infectious virus. No virus antigen-positive cells were detected beyond 14 passages. Once antiserum was removed from the seemingly "cured cultures", however, a small number of antigen-positive cells appeared and the release of infectious virus into the culture fluid resumed. Even after 67 passages (200 days) of culture in the presence of anti-serum, the virus reappeared in the culture. At least 0.01 per cent of L929 cells in cultures maintained under antiserum harbored the virus without expression of virus antigen. The virus recovered from such cells was temperature sensitive. The infection of fresh L929 cells with the variant led to noncytocidal persistent infection which was maintained by propagation of virus-infected cells. MuV carrier cultures could be cured by serial cultivation in medium containing the mixture of antiserum and IFN. When L-MuV cells were subcultured with medium containing neutralizing monoclonal antibodies (MoAbs), antibody-resistant variant viruses were rapidly generated and selected. In the presence of IFN variant viruses resistant to IFN were generated. In view of the small amount of virus produced from persistently infected cells, variant viruses appeared to be generated in an unusually high frequency in carrier cultures. Thus, this experimental system may offer a useful in vitro model for studying antigenic variation and generation of various variant viruses.