title: Human papillomavirus 16-encoded E7 protein inhibits IFN-γ-mediated MHC class I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in mouse keratinocytes.
abstract: Human papillomavirus 16 (HPV16) infection causes 50 % or more of cervical cancers in women. The HPV16 E7 oncogene is continuously expressed in infected epithelium with its oncogenicity linked to cervical cancer. The E7 protein is an ideal target in control of HPV infection through T-cell-mediated immunity. Using HPV16 E7-transgenic mouse keratinocytes (KCs-E7) to investigate T-cell-mediated immune responses, we have shown previously that HPV16-encoded E7 protein inhibits IFN-γ-mediated enhancement of MHC class I antigen processing and T-cell-induced target cell lysis. In this study, we found that HPV16 E7 suppresses IFN-γ-induced phosphorylation of STAT1((Tyr701)), leading to the blockade of interferon regulatory factor-1 (IRF-1) and transporter associated antigen processing subunit 1 (TAP-1) expression in KCs-E7. The results of a (51)Cr release assay demonstrated that IFN-γ-treated KCs-E7 escaped from CTL recognition because HPV16 E7 downregulated MHC class I antigen presentation on KCs. Restoration of IRF-1 expression in KCs-E7 overcame the inhibitory effect of E7 protein on IFN-γ-mediated CTL lysis and MHC class I antigen presentation on KCs. Our results suggest that HPV16 E7 interferes with the IFN-γ-mediated JAK1/JAK2/STAT1/IRF-1 signal transduction pathway and reduces the efficiency of peptide loading and MHC class I antigen presentation on KCs-E7. These results may reveal a new mechanism whereby HPV16 escapes from immune surveillance in vivo.
authors: Centre for Kidney Disease Research, Venomics Research, University of Queensland Medicine School, Transitional Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD 4102, Australia.
authors: Fang
authors: F
authors: Zhou
authors: Centre for Kidney Disease Research, Venomics Research, University of Queensland Medicine School, Transitional Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD 4102, Australia.
authors: JieZhong
authors: J
authors: Chen
authors: Centre for Kidney Disease Research, Venomics Research, University of Queensland Medicine School, Transitional Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD 4102, Australia.
authors: Kong-Nan
authors: KN
authors: Zhao
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D050856:Interferon Regulatory Factor-1; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma