Pathogenicity

The virus is not highly pathogenic in the immunocompetent host. Experimental pathogenicity of MCMV depends on several factors including dosage, virus strain, genetic susceptibility of the mouse, site of inoculation, and age of the mouse. Immunocompetent mice manifest minor illness when inoculated with a sublethal LD50. Virus continually passaged in tissue culture loses virulence. Commercially available mice may be genetically susceptible, moderately resistant, or resistant.

Virus titers following an intraperitoneal infection peak between days 5 and 7. Initial virus replication occurs in peritoneal macrophages and mesothelial cells and virus is subsequently disseminated by mononuclear cells to the liver and the spleen. Virus amplification in the reticuloendothelial organs precedes secondary viremia. Infected mononuclear cells infiltrate organs to initiate organ-specific infection. Resolution of the productive infection need not clear virus from organs which become chronically infected. Chronic infections may be persistent or latent. Persistently infected mice shed virus from saliva and urine, and virus may be recovered from explants of organ tissues in a time-dependent manner. The persistent infection wanes, and virus proliferation segues into a state of molecular latency in which the copy number of viral genomes per organ reflects the initial viral burden. In latent infection, viral footprints are detected by molecular analyses, or infectious virus is recovered after immunosuppression or by explantation/cocultivation/transplantation of infected tissues on permissive cell lines or into severe combined immunodeficient (SCID) mice. Primary infections in younger mice are more likely to establish latent infections than in older mice. In germ-free and specific pathogen-free mice, the indigenous bacterial flora influences the establishment of organ-specific latency. The extent of organ-specific, latent MCMV burden in immunocompetent, but not immunocompromised, mice reflects virus amplification during primary infection and augurs reactivation.

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