An experimental model for testing
antiviral agents against severe cytomegalovirus (CMV)
infection in immunocompromised hosts was developed. The model consisted of
cyclophosphamide (Cy) treatment of CMV-infected guinea pigs to simulate CMV
infection in immunodeficient individuals. Of the 3 Cy regimens tested, a single 300 mg/kg dose administered one day after virus inoculation resulted in the most severe CMV
infection considering mortality rates, mean day of death and loss of
body weight. Evaluation of responses to both T and B cell
mitogens suggested that the severe and lethal CMV
infection resulted from the combined immunosuppressive effect of Cy and CMV. The
nucleoside analog [9-(1-3-dihydroxy-2-propoxymethyl)
guanine (
DHPG) was used to assess the usefulness of the CMV-infected immunocompromised host model.
DHPG (100 mg/kg/day for 8 days) prevented death but did not reduce virus infectivity titers in blood of Cy-treated, CMV-infected guinea pigs. This model of CMV
infection in immunocompromised guinea pig is a relevant and convenient experimental tool for the assessment of candidate anti-CMV agents under well-defined experimental conditions, such as appropriate CMV inoculum and Cy regimen.