HUMAN CYTOMEGALOVIRUS BLOCKS INTERFERON-?? STIMULATED UP-REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I EXPRESSION AND THE CLASS I ANTIGEN PROCESSING MACHINERY1

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Abstract
Interferon-γ stimulates major histocompatibility complex (MHC) class I antigen processing and presentation by inducing the expression of major histocompatibility complex class I heavy chains, β2-microglobulin, the transporter associated with antigen processing, and components of the proteasome complex.We demonstrate that this effect of interferon-γ 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-γ 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-γ. Thus protected, human cytomegalovirus persists and may exacerbate graft rejection or lead to fulminant infection in the immunocompromised transplant recipient.