Abstract

The two major HPV-16 oncogenes, E6 and E7 are transcribed from the viral. p97 promoter, the activity of which is modulated by a complex network of transcriptional. elements located in the viral. Upstream Regulatory Region (URR). Genetic analysis of Bovine Papillomavirus (BPV) has shown that the viral. E2 gene product is an important regulator of viral. gene expression1,2and some studies have shown that the BPV E2 protein will repress transcription from the HPV-16 promoter3. A weak transcriptional. repressor activity has also been reported for the HPV-18 E2 protein4. In many late stage tumours and derived cell lines the HPV DNA Is often integrated into the host genome with concomitant loss of E2 coding sequences5. These observations gave rise to a hypothesis which suggested that integration and deletion of E2 regulatory activity was a prerequisite for late stage tumour progression. However, there are now several. reports6,7 of the existence of episomal. HPV-16 DNA capable of encoding full length E2 protein in late stage tumours. In addition, a recent HPV-16 isolate defective for keratinocyte immortalisation was shown to contain a mutation in the E2 gene; cotransfecting a wild type E2 restored the immortalising activity of this virus8.

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