Activation of cytomegalovirus infection in immunosuppressed cynomolgus monkeys inoculated with varicella-zoster virus.

Abstract

A systemic activated cytomegalovirus (CMV) infection was fortuitously detected in almost all monkeys which had been immunosuppressed with antithymocyte globulin (ATG), cyclophosphamide (CY), and cortisone acetate (CS) before and after experimental inoculation with varicella-zoster virus (VZV). They developed exudative pneumonia, and the lesions in visceral organs and tissues contained cytomegalic cells with intranuclear inclusion bodies, in which viral antigens, specific for CMV, but not inoculated VZV, were detected by immunofluorescence. Serological study of paired sera from these monkeys ascertained preexisting CMV infection. Under the present experimental conditions, this infection was highly reproducible and always occurred within three, but not two, weeks of immunosuppression in monkeys inoculated with VZV. We therefore examined the host factors involved in activation of latent CMV. The immunocompetence of the host was destroyed almost completely with treatment of ATG, CY, and CS, but not with combinations of two of these agents, revealing the systemic depletion of lymphoid cells in tissues including the thymus medulla. Although the role of VZV in the induction of CMV remains uncertain, the heterologous VZV inoculum may have produced some effects equivalent to the allogeneic reaction to release latent CMV. These monkeys may represent an animal model of "opportunistic" CMV infection in immunocompromised and/or allografted humans.