Human cytomegalovirus blocks interferon-gamma stimulated up-regulation of major histocompatibility complex class I expression and the class I antigenprocessing machinery
Dm. Miller et al., Human cytomegalovirus blocks interferon-gamma stimulated up-regulation of major histocompatibility complex class I expression and the class I antigenprocessing machinery, TRANSPLANT, 69(4), 2000, pp. 687-690
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.