title: Comparing effects of BK virus agnoprotein and herpes simplex-1 ICP47 on MHC-I and MHC-II expression.
abstract: BACKGROUND
  Among human polyomaviruses, only BK virus (BKV) and JC virus (JCV) encode an agnoprotein upstream of VP1 on the viral late transcript. BKV agnoprotein is abundantly expressed late in the viral life cycle, but specific cellular and humoral immune responses are low or absent. We hypothesized that agnoprotein might contribute to BKV immune evasion by downregulating HLA expression, similar to Herpes simplex virus-1 ICP47.
  
  
  METHODS
  UTA-6 or primary human renal proximal tubular epithelial cells (RPTEC) were co-transfected with plasmids constitutively expressing agnoprotein, or ICP47, and enhanced green-fluorescent protein (EGFP). EGFP-gated cells were analyzed for HLA-ABC and HLA-DR expression by flow cytometry. HLA-ABC and HLA-DR expression was also analyzed on UTA-6 bearing tetracycline-regulated agnoprotein or ICP47. Effects of agnoprotein on viral peptide-dependent T-cell killing were investigated using (51)Cr release.
  
  
  RESULTS
  ICP47 downregulated HLA-ABC without affecting HLA-DR, whereas agnoprotein did not affect HLA-ABC or HLA-DR expression. Interferon- γ treatment increased HLA-ABC in a dose-dependent manner, which was antagonized by ICP47, but not by agnoprotein. In UTA-6 cells, agnoprotein expression did neither impair HLA-ABC or -DR expression nor peptide-specific killing impaired by HLA-matched T-cells.
  
  
  CONCLUSIONS
  Unlike the HSV-1 ICP47, BKV agnoprotein does not contribute to viral immune evasion by down-regulating HLA-ABC, or interfere with HLA-DR expression or peptide-dependent T-cell cytotoxicity.
authors.affiliation: Transplantation & Clinical Virology, Department Biomedicine Haus Petersplatz, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
authors.forename: Michela
authors.initials: M
authors.lastname: Cioni
authors.forename: Christian
authors.initials: C
authors.lastname: Mittelholzer
authors.forename: Marion
authors.initials: M
authors.lastname: Wernli
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
mesh_terms: D001739:BK Virus / Q000502:physiology*; D045744:Cell Line, Tumor; D002469:Cell Separation; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D027601:Polyomavirus Infections / Q000276:immunology* / Q000821:virology; D018139:Simplexvirus / Q000502:physiology*; D019076:Transgenes / Q000235:genetics; D014412:Tumor Virus Infections; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D018406:Virus Physiological Phenomena; D000086082:Viroporin Proteins
chemical_list: D049452:Green Fluorescent Proteins; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017874:Immediate-Early Proteins; D054334:Viral Regulatory and Accessory Proteins; C105843:ICP47 protein, Herpes simplex virus; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins