Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection.

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorly understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL). We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins.