title: E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I.
abstract: Papillomaviruses have evolved mechanisms that result in escape from host immune surveillance. The E5 protein is expressed early in papillomavirus infection in the deep layers of the infected epithelium. It is localized to the Golgi apparatus (GA) and endoplasmic reticulum. The E5 protein of bovine papillomavirus (BPV) impairs the synthesis and stability of major histocompatibility (MHC) class I complexes and prevents their transport to the cell surface due to retention in the GA. Here we show that human papillomavirus type 16 (HPV-16) E5 also causes the retention of MHC (HLA) class I complexes in the GA and impedes their transport to the cell surface, which is rescued by treatment with interferon. Unlike BPV E5, HPV-16 E5 does not affect the synthesis of HLA class I heavy chains or the expression of the transporter associated with antigen processing TAP. These results show that downregulation of surface MHC class I molecules is common to both BPV and HPV E5 proteins. Moreover, we determined that HPV-16 E5 downregulates surface expression of HLA-A and HLA-B, which present viral peptides to MHC class I-restricted cytotoxic T lymphocytes (CTLs), but not the natural killer (NK) cell inhibitory ligands HLA-C and HLA-E. Selective downregulation of cell surface HLA class I molecules may allow the virus to establish infection by avoiding immune clearance of virus-infected cells by both CTLs and NK cells.
authors.affiliation: Institute of Comparative Medicine, Department of Pathological Sciences, Glasgow University, Glasgow G61 1QH, Scotland, UK.
authors.forename: G Hossein
authors.initials: GH
authors.lastname: Ashrafi
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Haghshenas
authors.forename: Barbara
authors.initials: B
authors.lastname: Marchetti
authors.forename: Philippa M
authors.initials: PM
authors.lastname: O'Brien
authors.forename: M Saveria
authors.initials: MS
authors.lastname: Campo
mesh_terms: D015536:Down-Regulation; D005347:Fibroblasts; D020869:Gene Expression Profiling; D006056:Golgi Apparatus / Q000502:physiology; D006680:HLA Antigens / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D015603:Keratinocytes; D007694:Killer Cells, Natural / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D027383:Papillomaviridae / Q000472:pathogenicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D000097625:HLA-E Antigens; D000086082:Viroporin Proteins
chemical_list: D006680:HLA Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D000097625:HLA-E Antigens; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins