Human cytomegalovirus blocks interferon-γ stimulated up-regulation of major histocompatibility complex class I expression and the class I antigen processing machinery

Interferon-gamma stimulates major histocompatibility complex (MHC) class I antigen processing and presentation by inducing the expression of major histocompatibility complex class I heavy chains, beta(2)-microglobulin, the transporter associated with antigen processing, and components of the proteasome complex. We demonstrate that this effect of interferon-gamma on the major histocompatibility complex class I pathway is inhibited in human cytomegalovirus-infected fibroblasts and endothelial cells. This is the result of a direct human cytomegalovirus/cell interaction leading to a block in interferon-gamma signal transduction beginning at early times after infection and peaking at 72 hr after infection. These observations suggest a novel level of herpesvirus interference with antigen processing: protection of infected cells from the immunoregulatory effects of interferon-gamma. Thus protected, human cytomegalovirus persists and may exacerbate graft rejection or lead to fulminant infection in the immunocompromised transplant recipient.