Down-regulation of surface major histocompatibility complex class I by guinea pig cytomegalovirus

Live attenuated strains of human cytomegalovirus are under development as vaccines to prevent birth defects resulting from congenital infections. These strains encode four proteins that inhibit surface expression of MHC class I, presumably to evade cytotoxic T-cell recognition and, perhaps, attenuate induction of immunity. To initiate studies of the role of class I down-regulation on congenital infection and vaccine efficacy, the ability of guinea pig cytomegalovirus to down-regulate class I was examined. Surface class I was specifically down-regulated on infected cells up to 8-fold. Sensitivity to UV irradiation and insensitivity to a viral DNA synthesis inhibitor revealed that immediate early or early viral gene(s) are responsible. Identification of these genes will permit future experiments to evaluate the role of class I down-regulation in congenital cytomegalovirus disease and its impact on vaccine efficacy. These findings should be pertinent to understanding human cytomegalovirus disease and may help guide the design of candidate vaccines.