High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

TY - JOUR

T1 - High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

AU - Bottley, G

AU - Watherston, O G

AU - Hiew, Y-L

AU - Norrild, B

AU - Cook, G P

AU - Blair, G E

N1 - Keywords: Cells, Cultured; Female; Hela Cells; Histocompatibility Antigens Class I; Human papillomavirus 16; Human papillomavirus 18; Humans; Killer Cells, Natural; Oncogene Proteins, Viral; Papillomavirus Infections; Tumor Escape; Uterine Cervical Neoplasms

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1038/sj.onc.1210798

DO - 10.1038/sj.onc.1210798

M3 - Journal article

C2 - 17828295

SN - 0950-9232

VL - 27

SP - 1794

EP - 1799

JO - Oncogene

JF - Oncogene

IS - 12

ER -