Efficient downregulation of major histocompatibility complex class I molecules in human epithelial cells infected with cytomegalovirus.
Liver and intestinal epithelial cells are a major target of infection by cytomegaloviruses (CMV), causing severe disease in affected organs of immunocompromised patients. CMV downregulates major histocompatibility complex class I (MHC-I) molecule expression in fibroblasts in order to avoid lysis by CD8(+) cytotoxic T lymphocytes. However, MHC-I expression in human cytomegalovirus (HCMV)-infected hepatic tissue was reported to be increased. As it is unclear at present whether HCMV affects MHC-I expression in epithelial cells, new cell culture models for HCMV infection of differentiated hepatobiliary cell lines were established. HCMV immediate early gene expression was achieved in 60 to 95% of cells. Progression of the HCMV replication cycle differed from prototypic infection of fibroblasts, since structural early and late proteins were produced at low levels and HCMV progeny yielded much lower titres in hepatobiliary cells. In contrast, HCMV glycoproteins, gpUS2, gpUS3, gpUS6 and gpUS11, that downregulate MHC-I expression were synthesized with temporal kinetics and in a similar quantity to that seen in fibroblasts. As a result, HCMV infection led to a drastic and selective downregulation of MHC-I expression in epithelial cells and was uniformly observed irrespective of the hepatic or biliary origin of the cells. The new models document for the first time a stealth function of HCMV in epithelial cells and indicate that the downregulation of MHC-I expression by HCMV can occur in the virtual absence of virus replication.
Benz
Christine
C
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9a, 80336 München, Germany1.
Reusch
Uwe
U
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9a, 80336 München, Germany1.
Muranyi
Walter
W
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9a, 80336 München, Germany1.
Brune
Wolfram
W
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9a, 80336 München, Germany1.
Atalay
Ramazan
R
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9a, 80336 München, Germany1.
Hengel
Hartmut
H
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9a, 80336 München, Germany1.
D001652:Bile Ducts / Q000821:virology; D003587:Cytomegalovirus / Q000502:physiology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000821:virology; D009928:Organ Specificity; D014764:Viral Proteins / Q000096:biosynthesis
D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins