EVIDENCE FOR THE SEPARATE REGULATION OF THE HUMAN-PAPILLOMAVIRUS TYPE-11 E7 AND E6 PROMOTERS BY VIRAL CIS SEQUENCES NEAR THE E6 PROMOTER

The human papillomavirus type 11 (HPV-11) 57 protein can modulate host cell functions and is required for papilloma formation, but little is known concerning the regulation of its expression. This study was des igned to determine whether the Viral upstream regulatory region contro lled expression from the E7 promoter and whether cia sequences differe ntially regulated E6 and E7 expression in laryngeal mucosal keratinocy tes, the natural target cells for this virus. Reporter constructs were designed to study expression of the luciferase gene from the HPV-11 E 7 promoter in its natural position downstream of a functional E6 promo ter. E7 expression, like E6 expression, required upstream regulatory s equences, However, E7 expression was less sensitive to repression by v iral E2 protein and to mutation of the Spl binding site adjacent to th e E2 binding site. Moreover, there was differential sensitivity of the two promoters to mutation of the E6 TATA hox, with E7 expression more affected than E6 expression. These findings show that, in the normal host cells for this virus, the E6 and E7 promoters can he independentl y regulated by the cis regulatory region adjacent to the E6 promoter. (C) 1998 Academic Press.