Relative enhancer activity and transforming potential of authentic human papillomavirus type 6 genomes from benign and malignant lesions

Abstract

Human papillomavirus type 6 (HPV-6) is predominantly associated with benign genital warts whereas HPV-16 and HPV-18 are detected predominantly in carcinomas of the lower genital tract; HPV-6 is found rarely in such carcinomas. Experiments were designed to discriminate between two hypotheses concerning the role of HPV-6 in the genesis of a genital tract carcinoma: (i) the HPV-6 in the carcinoma (HPV6-T70) differs genetically from HPV-6 in a benign lesion (HPV6-W50), giving HPV6-T70 properties similar to those of HPV-16/18: (ii) HPV6-T70 and HPV6-W50 have similar biological activity, suggesting that the role of HPV-6 in oncogenesis is different from that of HPV-16/18. Restriction enzyme digestion and DNA sequence determination established that HPV6-T70 differs from HPV6-W50 in the upstream regulatory region (URR) but not in the proteins encoded by open reading frames (ORFs) E5, E6 or E7, ORFs implicated in oncogenesis. To determine whether the difference in the URR sequence could alter the level of expression of viral genes, the URRs were cloned into the enhancerless plasmid pSVEcat. Analysis of chloramphenicol acetyltransferase activity after transfection into HeLa and Vero cells showed that the URRs had comparable enhancer activity. Cotransfection of baby rat kidney (BRK) cells with HPV6-T70 and an activated ras gene indicated that, in contrast to HPV-16 and HPV-18, this HPV-6 genome could not cooperate with ras to transform BRK cells. The data suggest that HPV6-T70 and HPV6-W50 have similar enhancer activity and transforming potential.