Human cytomegalovirus blocks interferon-gamma stimulated up-regulation of major histocompatibility complex class I expression and the class I antigenprocessing machinery

Interferon-gamma stimulates major histocompatibility complex (MHC) class I antigen processing and presentation by inducing the expression of major his tocompatibility complex class I heavy chains, beta(2)-microglobulin, the tr ansporter associated with antigen processing, and components of the proteas ome complex. We demonstrate that this effect of interferon-gamma on the maj or histocompatibility complex class I pathway is inhibited in human cytomeg alovirus-infected fibroblasts and endothelial cells. This is the result of a direct human cytomegalovirus/cell interaction leading to a block in inter feron-gamma signal transduction beginning at early times after infection an d peaking at 72 hr after infection. These observations suggest a novel leve l of herpesvirus interference with antigen processing: protection of infect ed cells from the immunoregulatory effects of interferon-gamma. Thus protec ted, human cytomegalovirus persists and may exacerbate graft rejection or l ead to fulminant infection in the immunocompromised transplant recipient.