Identification of a promoter in position 56 within the long control regionof human papillomavirus type 18

The expression of the oncogenes E6 and E7 of the cervical cancer associated human papillomavirus type 18 was shown to be directed from the promoter in position 105 (P-105), which is reportedly: the only early promoter located within the long control region (LCR). However, in C33A cells transiently t ransfected with a reporter construct containing the LCR of HPV18 in front o f the luciferase gene a transcript initiating at position 56 was present in addition to those initiating from the P-105, A perfect TATA Box consensus sequence 30 bp further upstream, which is highly conserved among HPVs assoc iated with cervical cancer, was required for the activity of this novel pro moter, denoted here as P-56. The P-56 specific transcript obviously depends on promoter downstream sequences, since transcripts initiating from the P- 56 were not present when the CAT gene was cloned downstream of the LCR. We detected transcripts initiating from both the P-105 and the P-56 in primary keratinocytes harboring, episomal HPV18 as well as in the HPV 18 positive cervical carcinoma cell lines HeLa, C4-1 and SW756. Our data suggest that i n HPV 18, the expression of the early viral proteins including the oncogene s might be directed from a second promoter, located within the LCR.