Virulence and attenuation of murine cytomegalovirus

Abstract

Murine cytomegalovirus (MCMV) was rapidly and regularly attenuated by passage through mouse embryo cell culture. This attenuation was manifested by alteration of lethality for suckling mice and by a striking loss of capacity to multiply in liver and spleen of weanling mice. The attenuation was selective in that the passaged virus multiplied vigorously in other organs and established high titer infections in submaxillary glands and pancreas comparable to those seen with wild virus. Furthermore, attenuated virus no longer induced transient suppression of antibody and interferon responsiveness which was a regular feature of wild MCMV infection. Wild and attenuated MCMV shared the property of being poor immunogens. They induced anti-CMV complement-fixing or neutralizing antibody very slowly with barely detectable levels present at the end of the first 2 weeks of infection. The close antigenic relationship between wild and attenuated agents was demonstrated by nearly identical neutralization by a rabbit antiserum induced with wild MCMV. Furthermore, survivors of neonatal infection with attenuated virus were fully protected against subsequent challenge with potentially lethal doses of wild MCMV. Virulence could be rapidly restored by back passage in mice.