Human papillomavirus 16-encoded E7 protein inhibits IFN-gamma-mediated MHC class I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in mouse keratinocytes

Zhou, Fang, Chen, JieZhong and Zhao, Kong-Nan (2013) Human papillomavirus 16-encoded E7 protein inhibits IFN-gamma-mediated MHC class I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in mouse keratinocytes. Journal of General Virology, 94 Pt. 11: 2504-2514. doi:10.1099/vir.0.054486-0


Author Zhou, Fang
Chen, JieZhong
Zhao, Kong-Nan
Title Human papillomavirus 16-encoded E7 protein inhibits IFN-gamma-mediated MHC class I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in mouse keratinocytes
Formatted 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
Journal name Journal of General Virology   Check publisher's open access policy
ISSN 0022-1317
1465-2099
Publication date 2013-11-01
Sub-type Article (original research)
DOI 10.1099/vir.0.054486-0
Open Access Status
Volume 94
Issue Pt. 11
Start page 2504
End page 2514
Total pages 11
Place of publication Spencers Wood, Reading, Berks, United Kingdom
Publisher Society for General Microbiology
Language eng
Subject 2406 Virology
Formatted 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 51Cr 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
 
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