Epstein-Barr virus provides a survival factor to Burkitt's lymphomas.
Epstein-Barr virus (EBV) has been causally associated with at least five human malignancies. The exact contributions made by EBV to these cancers remain unknown. We demonstrate that one viral protein found in all EBV-associated malignancies, Epstein-Barr nuclear antigen 1 (EBNA-1), is required for survival of one of these cancers, EBV-positive Burkitt's lymphoma. Inhibition of EBNA-1 decreases survival of these tumor cells by inducing apoptosis. Expression of EBNA-1 in uninfected cells also can inhibit apoptosis induced by expression of p53 in the absence of the EBV genome. Our findings demonstrate that EBNA-1 is critical for the continued survival of EBV-associated Burkitt's lymphoma, and, by extension, for the other B cell tumors with which EBV is associated. Efficient inhibitors of EBNA-1's functions would likely prove useful in the therapy of EBV-associated malignancies.
Kennedy
Gregory
G
McArdle Laboratory for Cancer Research and Department of Surgery, University of Wisconsin, 1400 University Avenue, Madison, WI 53706, USA.
Komano
Jun
J
Sugden
Bill
B
D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology; D002051:Burkitt Lymphoma / Q000473:pathology* / Q000821:virology*; D002460:Cell Line; D002470:Cell Survival; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000502:physiology; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D017384:Sequence Deletion; D014161:Transduction, Genetic
D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1