We have examined the possibility that the E7 proteins of the high-risk human papillomavirus (HPV) type 16 and 18 and the oncogenic adenovirus (Ad) type 12 E1A protein share the ability to down-regulate the expression of components of the antigen processing and presentation pathway, as a common strategy in the evasion of immune surveillance during the induction of cell transformation. Expression of the HPV 18 E7 oncoprotein, like Ad 12 E1A, resulted in repression of the major histocompatibility complex (MHC) class I heavy chain promoter, as well as repression of a bidirectional promoter that regulates expression of the genes encoding the transporter associated with antigen processing subunit 1 (TAP1) and a proteasome subunit, low molecular weight protein 2 (LMP2). HPV 16 E7 also caused a reduction in class I heavy chain promoter activity, however it did not have any significant effect on the activity of the bidirectional promoter. Interestingly, expression of the low-risk HPV 6b E7 protein resulted in an increase in MHC class I heavy chain promoter activity, while repressing the TAP1/LMP2 promoter. Interference with the class I pathway could also explain the ability of low-risk HPVs in inducing benign lesions.
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We would like to thank JT Schiller (National Cancer Institute, USA) for kindly providing the HPV 6b, 16 and 18 E7 expression vectors. The pE2ACAT construct was a kind gift from MB Mathews (University of Medicine and Dentistry, New Jersey at Newark, USA). We would also like to thank Lindsay J Stanbridge and Luke Stockwin for helpful discussions. This work was supported by Yorkshire Cancer Research.
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Georgopoulos, N., Proffitt, J. & Blair, G. Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins. Oncogene 19, 4930–4935 (2000). https://doi.org/10.1038/sj.onc.1203860
- human papillomavirus
- MHC class I
- transcriptional repression
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