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

• Published in: Transplantation Vol. 69; no. 4; pp. 687 - 690
• Main Authors: Miller, D M, Zhang, Y, Rahill, B M, Kazor, K, Rofagha, S, Eckel, J J, Sedmak, D D
• Format: Journal Article
• Language: English
• Published: United States 27-02-2000
• Subjects: Antigen Presentation - drug effects; Antigen Presentation - physiology; Cytomegalovirus Infections - physiopathology; Electrophoresis; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - virology; Fibroblasts - immunology; Fibroblasts - metabolism; Fibroblasts - virology; g-Interferon; Gene Expression; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - physiology; Human cytomegalovirus; Humans; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - genetics; Interferon-gamma - pharmacology; Kinetics; Signal Transduction - drug effects; Up-Regulation - drug effects
• ISSN: 0041-1337
• DOI: 10.1097/00007890-200002270-00040

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, beta2-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.