Resistance of human cells to the adenovirus E3 effect on class I MHC antigen expression. Implications for antiviral immunity.
Group C human adenovirus (Ad) serotypes (e.g., Ad2 and Ad5) cause persistent infections in man. One proposed mechanisms to explain human adenovirus persistence is an ineffective CTL response due to reduced cell surface expression of class I MHC Ag on virally infected cells, an effect mediated by the 19-kDa glycoprotein encoded by Ad early region 3 (E3). In the present study, the generality of this phenomenon was tested by analyzing E3 19-kDa glycoprotein down-regulation of cell surface class 1 MHC Ag on a variety of human cell types. With the exception of the Ad5 early region 1 (E1) transformed cell line, 293, Ad2/5 infection of fibroblastic, epithelial, and lymphoid cells did not cause major decreases in surface class I Ag until the terminal stages of infection when cell death is imminent. Furthermore, newly synthesized class I Ag continued to be surface expressed on most cell types at times when infected cells contained large amounts of Ad E3 19-kDa glycoprotein. These data indicate that most types of human cells are resistant to the E3 19-kDa glycoprotein effect, suggesting that virus-specific CTL recognition and lysis of most Ad2/5-infected human cells should not be limited by E3 19-kDa-mediated reduction in class I MHC Ag expression.
Routes
J M
JM
Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Cook
J L
JL
D000257:Adenoviridae Infections / Q000276:immunology*; D017456:Adenovirus Early Proteins; D000258:Adenovirus Infections, Human / Q000276:immunology*; D000260:Adenoviruses, Human / Q000276:immunology*; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005347:Fibroblasts / Q000382:microbiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000382:microbiology; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D013997:Time Factors; D014779:Virus Replication
D017456:Adenovirus Early Proteins; D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; C018315:hexon capsid protein, Adenovirus