High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells
High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells
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DOI：
10.1038/sj.onc.1210798
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发表时间：
2008-03-13
期刊：
影响因子：
8
通讯作者：
Blair, G. E.
中科院分区：
文献类型：
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作者：
Bottley, G.;Watherston, O. G.;Blair, G. E.
高危型人乳头瘤病毒（HPV）是宫颈癌的主要致病因素，E6和E7基因编码主要的HPV癌蛋白。高危型HPV的E7蛋白改变细胞周期进程，并抑制编码抗原呈递途径组分的基因，这表明E7在肿瘤免疫逃逸中起作用。我们发现通过RNA干扰敲低HPV16和HPV18转化的宫颈癌细胞中E7的表达，会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。四环素调控诱导HPV16 E7会导致细胞表面MHC I类分子表达降低以及NK细胞杀伤作用增强。我们的研究结果表明，对于HPV相关的恶性肿瘤，MHC I类分子表达降低是一种主动免疫逃逸策略的结果，这种策略已经进化以协助病毒复制。
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.