Identification of DNA-protein interactions and enhancer activity at the 5' end of the upstream regulatory region in human papillomavirus type 11

Abstract

We have examined the 5' end of the noncoding region of the genome of a human papillomavirus, HPV-11, for regulatory elements using permissive host cells. This region of unknown function in the upstream regulatory region (URR) is known to have unusual DNA structure and frequently contains rearrangements which are associated with some more virulent isolates. This 5' 269-bp fragment was found to exhibit both specific DNA-protein binding using laryngeal papilloma protein extracts and enhancer activity in normal and papillomatous primary laryngeal cells. The viral DNA flanks the L1 open reading frame and does not contain the viral E2 binding site. Three distinct protein binding sites are contained in a 50-bp region of the fragment. This fragment, as a whole, functions as an enhancer in primary laryngeal and papilloma cells when ligated to the SV40 promoter and SV40 T-antigen gene. We conclude that this part of the noncoding region of the papillomaviruses has elements characteristic of regulatory elements in cells permissive for infection by these viruses.