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

We have examined the possibility that the E7 proteins of the high-risk huma n papillomavirus (HPV) type 16 and 18 and the oncogenic adenovirus (Ad) typ e 12 E1A protein share the ability to down-regulate the expression of compo nents of the antigen processing and presentation pathway, as a common strat egy in the evasion of immune surveillance during the induction of cell tran sformation. Expression of the HPV 18 E7 oncoprotein, like Ad 12 E1A, result ed in repression of the major histocompatibility complex (MHC) class I heav y chain promoter, as well as repression of a bidirectional promoter that re gulates expression of the genes encoding the transporter associated with an tigen processing subunit 1 (TAP1) and a proteasome subunit, low molecular w eight 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 th e low-risk I-IPV 6b E7 protein resulted in an increase in MHC class I heavy chain promoter activity, while repressing the TAP1/LMP2 promoter, Interfer ence with the class I pathway could also explain the ability of low-risk HP Vs in inducing benign lesions.