Human cytomegalovirus binding to heparan sulfate proteoglycans on the cell surface and/or entry stimulates the expression of human leukocyte antigen class I.
Human cytomegalovirus (HCMV) is known to down-regulate the expression of human leukocyte antigen (HLA) class I, the process of which involves a subset of virus genes. Infection of human foreskin fibroblast (HFF) cells with UV-inactivated HCMV (UV-HCMV), however, resulted in an increase in HLA class I presentation on the cell surface in the absence of HCMV gene expression. Heparin, which inhibits the interaction of virus particles with cell surface heparan sulfate proteoglycans (HSPGs), blocked the effect of UV-HCMV on HLA class I expression. Pretreatment of cells with heparinase I decreased in a dose-dependent manner the effect of UV-HCMV on HLA class I expression enhancement. Sodium chlorate, which is known to inhibit the sulfation of HSPGs, gave a similar result. Pretreatment of UV-HCMV with trypsin or monoclonal antibody reactive with the envelope glycoprotein gB reduced the increase in HLA class I expression on the HFF cell surface by UV-HCMV. RT-PCR analysis demonstrated that the increase in HLA class I presentation on the HFF cell surface was due to an increase in HLA class I transcription. Thus, binding of HCMV particles to cell surface HSPGs appears to be required for the stimulation of HLA class I expression. It is also possible that virus entry, in addition to binding to HSPGs, may be involved in the stimulation of HLA class I expression, since the UV-HCMV entered the cells and all treatments to block virus binding to HSPGs would necessarily prevent virus entry.
Song
Byung H
BH
Division of Life Sciences, College of Natural Sciences1 and Research Institute for Genetic Engineering2, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Lee
Gyu C
GC
Division of Life Sciences, College of Natural Sciences1 and Research Institute for Genetic Engineering2, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Moon
Myung S
MS
Division of Life Sciences, College of Natural Sciences1 and Research Institute for Genetic Engineering2, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Cho
Yeon H
YH
Division of Life Sciences, College of Natural Sciences1 and Research Institute for Genetic Engineering2, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Lee
Chan H
CH
Division of Life Sciences, College of Natural Sciences1 and Research Institute for Genetic Engineering2, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000502:physiology; D014765:Viral Vaccines / Q000276:immunology
D019812:Heparan Sulfate Proteoglycans; D015395:Histocompatibility Antigens Class I; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040495:glycoprotein B, Simplexvirus