FIG. 5.
Virus replication and dissemination in vivo. Virus growth curves are shown as log-linear plots of infection load on the ordinate and time after infection on the abscissa. Infection loads in plantar tissue, spleen, and liver were determined at the indicated time points after subcutaneous, intraplantar infection of 7-Gy total-body γ-irradiated BALB/c recipients with 105 PFU (corresponds to ∼5 × 107 viral genomes) of the BAC-derived mCMVs indicated. In plantar tissue and in the spleen, the viral loads per 106 tissue cells were quantified by real-time PCR specific for viral gene M55 (gB) normalized to the cellular gene pthrp. Infection of the liver was quantified by counting infected liver cells, which are mostly hepatocytes and some endothelial cells, in representative 10-mm2 areas of tissue sections. Infection of cells was identified by immunohistological staining of intranuclear IE1 protein. Dots represent data from three individual mice per time point, with median values marked. The DTs (95% confidence intervals of DTs are in parentheses) were calculated by log-linear regression analysis. Note that DNA load present on day 1 in plantar tissue (arrows) mostly represents DNA of the virus inoculum. Accordingly, data for day 1 in plantar tissue were excluded from the regression analysis of virus replication. The time point of first detection of infected liver cells is revealed by the intersection between the calculated regression line and ordinate 0 (corresponds to one infected cell per test area), which was between days 3 and 4 for all viruses tested. The horizontal bars indicate the corresponding 95% confidence intervals.