Human cytomegalovirus blocks interferon-gamma 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, 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.
Miller
D M
DM
Department of Pathology, The Ohio State University, Columbus 43210, USA.
Zhang
Y
Y
Rahill
B M
BM
Kazor
K
K
Rofagha
S
S
Eckel
J J
JJ
Sedmak
D D
DD
D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000503:physiopathology*; D004586:Electrophoresis; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology*; D007700:Kinetics; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma