Effective antiviral chemotherapy in cytomegalovirus infection of mice

Both murine and human strains of cytomegalovirus were shown to be sensitive to the antiviral effects of adenine arabinoside and phosphonoacetic acid in tissue culture. In mice with lethal cytomegalovirus infections, treatment with adenine arabinoside (either 500 mg/kg intraperitoneally once daily or 250 mg/kg intraperitoneally twice daily for seven days) failed to reduce the mortality rate or to decrease the mean number of days until death. In contrast, treatment with the same dosage regimen of phosphonoacetic acid significantly reduced the mortality rate and decreased the mean number of days until death even when therapy was delayed for 24 hr. Although early treatment with phosphonoacetic acid resulted in a marked reduction in viral titers in the brains and lungs of infected mice, the major reason for efficacy appeared to be complete inhibition of viral replication in the liver. The observation that titers of complement-requiring neutralizing antibody were significantly lower in treated animals than in untreated controls is further evidence of successful therapy. Treatment of a nonlethal cytomegalovirus infection with phosphonoacetic acid beginning 48 hr after viral challenge resulted in elimination of clinical signs of illness and reduction in viral titers in tissues. These results indicate that phosphonoacetic acid is successful in the treatment of murine infections with cytomegalovirus; they suggest that this drug should be considered for potential use in serious cytomegalovirus infections in humans.