Ganciclovir treatment of murine cytomegalovirus infection in mice immunosuppressed by prior infection with Friend leukaemia virus
Antiviral Chemistry & Chemotherapy
Since many of the severe cytomegalovirus infections in humans occur in individuals immunosuppressed by the human immunodeficiency virus, we developed an analogous murine model for studying this disease. BALB/c mice infected with the Friend retrovirus complex (FV) were immunosuppressed (i.e., exhibited reduced spleen-cell mitogenic responses and natural killer cell activity) by 21 days after FV inoculation. Challenge with murine cytomegalovirus (MCMV) at that time led to mortality at doses generally non-lethal to normal mice. Superinfection of FV-infected mice with MCMV reduced spleen cell FV infectious centres and splenomegaly, and extended the lives of mice surviving the MCMV infection. Once-daily ganciclovir treatments of 12.5,25, and 50 mg kg−1 given to dually-infected mice for 5 days starting 24 h after MCMV inoculation resulted in 90–100% survival at 14 days (relative to MCMV inoculation) compared to 15% survival in the placebo group. By 70 days, survival in the drug-treated and placebo groups were 0–5%, these deaths being attributed to FV disease. Ganciclovir treatments reduced MCMV titres in spleen, liver, and kidney during treatment (day 4 of the infection), but lung and salivary gland titres rose between days 7 and 13 in surviving animals. Improved concanavalin A-induced mitogenic responses were noted on day 4 in mice treated with 25 and 50 mg kg−1. These results indicate that the FV/MCMV dual infection in mice can be used as a model for evaluating antiviral agents. Because of the complex nature of the interaction between FV and MCMV, the model may be more appropriate for advanced studies of well-defined viral inhibitors than for routine screening of potential new compounds.
Smee, D. F., A. Pease, R. A. Burger, J. H. Huffman, J. D. Morrey, K. M. Okleberry, R. L. Noble, and R. W. Sidwell. 1992. Ganciclovir treatment of murine cytomegalovirus infection in mice immunosuppressed by prior infection with Friend leukaemia virus. Antiviral Chemistry & Chemotherapy 3:327-333.