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Updated: Aug 9, 2026
Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Virulence and attenuation of murine cytomegalovirus
1Departments of Pediatrics and Medical Microbiology, University of Wisconsin Medical School, Madison, Wisconsin 53706.
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.
Insights
Murine cytomegalovirus (MCMV) passage in cell culture attenuates its virulence in mice. This attenuated MCMV selectively infects organs, is a poor immunogen, but still protects against wild MCMV infection.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Murine cytomegalovirus (MCMV) is a common pathogen with significant virulence in mice.
- Understanding MCMV attenuation is crucial for developing safer viral vectors and vaccines.
Purpose of the Study:
- To investigate the effects of serial passage in mouse embryo cell culture on MCMV virulence and immunogenicity.
- To characterize the biological and immunological properties of attenuated MCMV strains.
Main Methods:
- Serial passage of MCMV in mouse embryo cell culture.
- Assessment of viral lethality and organ-specific replication in suckling and weanling mice.
- Evaluation of immune responses (antibody and interferon) and protection against wild-type MCMV challenge.
Main Results:
- Passage rapidly attenuated MCMV, reducing lethality and replication in liver and spleen but not submaxillary glands or pancreas.
- Attenuated MCMV failed to induce transient immune suppression seen with wild-type MCMV.
- Both wild-type and attenuated MCMV were poor immunogens, inducing slow antibody responses.
- Attenuated MCMV conferred full protection against lethal wild-type MCMV challenge, with virulence restored upon back passage in mice.
Conclusions:
- Serial cell culture passage effectively attenuates MCMV virulence while maintaining selective organ tropism.
- Attenuated MCMV represents a potentially valuable tool, demonstrating protective immunity without causing significant immune suppression.
- Further research into MCMV attenuation mechanisms could inform vaccine development and gene therapy applications.
