NOVEL HYPOTHESES FOR THE ROLES OF EBNA-1 AND BHRF1 IN EBV-RELATED CANCERS

Epstein-Barr virus has been linked to several types of human cancer in cluding Burkitt's lymphoma and nasopharyngeal carcinoma but the mechan isms by which the virus might contribute to cancer remain obscure. Her e we consider the possibility that EBNA-1, which is expressed in both tumours, directly transactivates cell genes. The EBNA-1 protein was te sted for transcription transactivation domains and the human genome wa s screened for high-affinity EBNA-1-binding sites that might mediate t ransactivation. None were found, although novel low-affinity-binding s ites in the EBV genome were detected. We also investigated the express ion of BHRF1, the viral homologue to bcl-2, in epithelial cells and sh owed that it is expressed in vivo in the EBV replication found in oral hairy leukoplakia. A novel hypothesis is proposed for nasopharyngeal carcinoma in which BHRF1 expression protects cells against apoptotic d eath caused by environmental DNA damaging agents and thus contributes to the early stages of cancer development.