Activation of latent murine cytomegalovirus infection: cocultivation, cell transfer, and the effect of immunosuppression.

No free virus was detectable in any organ of DBA/2 mice greater than or equal to 16 weeks after infection with murine cytomegalovirus. Spleens were free of free lytic virus six weeks after infection. Spleen cells from such mice were shown to be latently infected by three methods. First, virus was recovered by cocultivation of spleen cells for two weeks or longer on either syngeneic or allogeneic (CDI) embryonic fibroblast cultures. Second, virus was recovered from salivary glands of either syngeneic (DBA/2) or allogeneic (C57BL/10) mice that received 10(8) spleen cells. Recovery was enhanced by treatment of allogeneic recipients with cyclophosphamide but not with azathioprine. Third, latently infected mice, after treatment with either cyclophosphamide or azathioprine, developed free murine cytomegalovirus in their salivary glands. The last two findings parallel observations of human cytomegalovirus in immunosuppressed patients and in patients receiving latently infected cells during transplantation. Both cyclophosphamide and azathioprine elevated titers of free lytic virus in the salivary glands.