Effects of cell source, mouse strain, and immunosuppressive treatment on production of virulent and attenuated murine cytomegalovirus

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Abstract
Murine cytomegalovirus pools from various in vitro and in vivo sources were compared for virulence in suckling mice in an effort to identify the conditions which were necessary for the production of virulent and attenuated viruses. Virus passaged in tracheal ring and salivary gland organ cultures, where virus is produced primarily by epithelial cells, was even more attenuated than virus passaged in mouse embryo fibroblasts. The attenuation observed after passage in all three of these in vitro systems did not appear to be due to defective interfering particles. We also found that virus produced in vivo in salivary glands became attenuated with time after infection. Virus harvested from salivary glands 5 to 6 weeks after infection was highly attenuated compared with both salivary gland-passaged virus harvested 2 to 3 weeks after infection and tissue culture-passaged virus. The attenuation of salivary gland-passaged virus with time was reversed when animals were treated with cyclophosphamide before the virus was harvested. A comparison of virus pools harvested from susceptible and resistant mouse strains indicated that the mouse strain had little effect on the virulence of the virus produced. When the various sources of virus tested in this study were ranked in terms of the virulence of the virus produced, salivary glands in intact mice either 2 to 3 weeks after infection or after cyclophosphamide treatment produced the most virulent virus, followed by mouse embryo fibroblast cultures, tracheal ring and salivary gland organ cultures, and, finally, salivary glands in intact mice 5 to 6 weeks after infection.