Use of temperature-sensitive mutants of mouse cytomegalovirus as vaccines

Abstract

Three temperature-sensitive (ts) mutants of mouse cytomegalovirus (MCMV) were compared with parent virus for their ability to produce acute infection, to stimulate protection against a lethal challenge with salivary gland MCMV, and to become latent and then be reactivated. During the acute phase of infection, ts mutant virus demonstrated very limited replication. During the later phase of infection (seven to 14 days after challenge), titers of virus in the pancreas and salivary glands in mice infected with parent virus continued to rise, whereas no virus could be detected in mice infected with the ts mutants. Prior infection with parent virus or the ts mutants protected susceptible mice from a lethal dose of salivary gland MCMV. One year after infection, treatment of mice with an immunosuppressive regimen resulted in reactivation of parent and ts mutant virus. Reactivated virus recovered from mice infected with ts mutant virus remained temperature sensitive.