Bottley G, Watherston O G, Hiew Y-L, Norrild B, Cook G P, Blair G E
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Oncogene. 2008 Mar 13;27(12):1794-9. doi: 10.1038/sj.onc.1210798. Epub 2007 Sep 10.
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.
高危型人乳头瘤病毒（HPV）是宫颈癌的主要致病因子，E6和E7基因编码主要的HPV癌蛋白。高危型HPV的E7蛋白会改变细胞周期进程，并抑制抗原呈递途径相关成分的编码基因，这表明E7在肿瘤免疫逃逸中发挥作用。我们发现，通过RNA干扰降低HPV16和HPV18转化的宫颈癌细胞中E7的表达，可增加细胞表面主要组织相容性复合体（MHC）I类分子的表达，并降低这些细胞对自然杀伤（NK）细胞的敏感性。四环素调控的HPV16 E7诱导导致细胞表面MHC I类分子表达降低，NK细胞杀伤作用增强。我们的结果表明，对于HPV相关的恶性肿瘤，MHC I类分子表达降低是一种为协助病毒复制而进化出的主动免疫逃逸策略的结果。
