1. ¹Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
2. ²Institute of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Copenhagen N, Denmark
3. ³Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK

Correspondence: Dr GE Blair, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, Garstang Building Room 8.10a, University of Leeds, Mount Preston Street, Leeds, W Yorks LS2 9JT, UK. E-mail: g.e.blair@leeds.ac.uk

Received 14 August 2006; Revised 2 August 2007; Accepted 15 August 2007; Published online 10 September 2007.

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.