Duplication of enhancer sequences in human papillomavirus 6 from condylomas of the mamilla

Abstract

Human papillomavirus (HPV) 6 usually induces tumors of the genital, oral, or laryngeal mucosa. An HPV 6-related DNA of 8.2 kb was detected in an extrachromosomal state in atypically located condylomas of the mamilla and was molecularly cloned. The identity of the cloned HPV DNA and the viral DNA in the biopsy was confirmed by comparative Pstl cleavage analysis, which showed typical HPV 6 DNA fragment patterns except for 0.2-kb larger B fragments. Sequencing revealed an exact 236-bp duplication encompassing nucleotides 7681 to 7896 of HPV 6b. This tandem repeat is just upstream from the putative early promoter and contains a 20-bp insertion at position 7720, which constitutes an enhancer element described by R. F. Rando, W. D. Lancaster, P. Han, and C. Lopez (Virology 155, 545-556, 1986). A Hinfl-Pstl fragment containing the whole duplication was cloned into an enhancer-dependent CAT expression vector and led to three- to sevenfold increased CAT activity when compared with the monomeric sequence in C127 cells and BPV1 transformed C127 cells. This indicates that the duplication within the HPV 6 isolate from the mamilla may influence early gene expression and possibly tissue tropism.