title: High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells.
abstract: High-risk human papillomavirus (HPV) is a major causative agent of cervical cancer and the E6 and E7 genes encode the major HPV oncoproteins. The E7 protein from high-risk HPV types alters cell cycle progression and represses genes encoding components of the antigen-presentation pathway, suggesting a role for E7 in tumour immune evasion. We show that knockdown of E7 expression in HPV16- and HPV18-transformed cervical carcinoma cells by RNA interference increased expression of major histocompatibility complex (MHC) class I at the cell surface and reduced susceptibility of these cells to natural killer (NK) cells. Tetracycline-regulated induction of HPV16 E7 resulted in reduced expression of cell surface MHC class I molecules and increased NK cell killing. Our results suggest that, for HPV-associated malignancies, reduced MHC class I expression is the result of an active immune evasion strategy that has evolved to assist viral replication.
authors.affiliation: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
authors.forename: G
authors.initials: G
authors.lastname: Bottley
authors.forename: O G
authors.initials: OG
authors.lastname: Watherston
authors.forename: Y-L
authors.initials: YL
authors.lastname: Hiew
authors.forename: B
authors.initials: B
authors.lastname: Norrild
authors.forename: G P
authors.initials: GP
authors.lastname: Cook
authors.forename: G E
authors.initials: GE
authors.lastname: Blair
mesh_terms: D002478:Cells, Cultured; D005260:Female; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology