Functional significance of sequence variation in the E2 gene and the long control region of human papillomavirus type 16

The long control region (LCR) and the E2 protein of human papillomaviruses (HPV) are the most important viral factors regulating transcription of the viral oncogenes E6 and E7. Sequence variation within these genomic regions may have an impact on the oncogenic potential of the virus. Sequence variat ion in the LCR and in the E2 gene of human papillomavirus type 16 (HPV-16) isolates originating from cervical cancer patients from East Hungary was st udied. In 30 samples, sequencing and/or single-strand conformation polymorp hism analysis revealed variants belonging to the European variant lineage o f HPV-16. These variants differed from the reference European clone only sl ightly in their E2 and LCR sequences. Three samples represented variants be longing to the Asian-American group. These differed from the published refe rence sequence at several positions in the LCR and E2 regions. Compared to the reference clone, the LCR clones of the European isolates showed very si milar transcriptional activities, while that of an Asian-American isolate h ad similar to 1.7-fold increased activity. Most of the increased activity o f the Asian-American isolate could be ascribed to nucleotide changes found at the 3' end of the LCR (nt 7660-7890). The transcriptional transactivatio n potentials of the HPV-16 E2 isolates differed only slightly from each oth er, and the differences seemed to be independent of the taxonomic position of the isolates.