C. Kammer et al., Sequence analysis of the long control region of human papillomavirus type 16 variants and functional consequences for P97 promoter activity, J GEN VIROL, 81, 2000, pp. 1975-1981
Genital human papillomaviruses (HPV) are considered to be one of the main r
isk factors for the development of cervical cancer. The P97 promoter at the
E6-proximal end of the long control region (LCR) regulates the transcripti
on of viral genes, especially the oncogenes E6 and E7. The LCR contains bin
ding sites of several viral and cellular transcription factors, which eithe
r activate or repress the P97 promoter. Intratype variants of HPV-16 belong
to six geographically clustered phylogenetic groups distributed all over t
he world. These variants exhibit differences in E6 protein activities and i
n tumour progression in vivo. Seven HPV-16 variants were investigated by se
quencing the entire LCR (nt 7060-124) and by comparing the transcriptional
activities of their P97 promoters. Previously unknown nucleotide variations
were identified in all LCRs investigated. In luciferase assays, 3.3- and 2
.8-fold increases in P97 promoter activity were detected in the Asian Ameri
can c and North American 1 variants when compared with the European referen
ce clone. The African variants 1a and 2a exhibited P97 promoter activities
comparable to the European reference clone. After recombining different LCR
fragments, the region responsible for enhanced transcription in the Asian
American c and North American 1 variants could be attributed to the E6-prox
imal end of the LCR (nt 7619-124).