The Epstein—Barr Virus Gene BHRF1, a Homologue of the Cellular Oncogene Bcl-2, Inhibits Apoptosis Induced by Gamma Radiation and Chemotherapeutic Drugs

  • N. J. McCarthy
  • S. A. Hazlewood
  • D. S. Huen
  • A. B. Rickinson
  • G. T. Williams
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)

Abstract

Analysis of apoptosis, active and controllable cell death, has demonstrated that the size of a cell population can be regulated by changes in the cell death rate as well as in the rates of proliferation and differentiation. Factors which alter the rate of cell death, such as expression of the proto-oncogene bc1-2, can therefore directly affect the number of cells within a population. Bc1-2 has been. shown to suppress apoptosis in response to a variety of stimuli and to act as a complementary survival signal for the random acquisition of other oncogenic mutations, such as deregulated c-myc.

The Epstein Barr virus (EBV) gene BHRF1 was the first of a family of bc1-2 homologues now being identified. BHRF1 and bc1-2 share 25% primary amino acid sequence homology. Here we show that γ radiation and several cytotoxic anticancer agents induce apoptosis in Burkitt’s lymphoma (BL) cell lines, as has been found in several other systems. Using gene transfection studies we have also shown that expression of either BHRF 1 or bc1-2 in BL cell lines significantly suppresses apoptosis in response to a variety of anticancer treatments. This has confirmed that BHRF 1 is functionally homologous to bcl-2 in B-cells and suggests that BHRF1 may act to prevent apoptosis during EBV infection, maximising virus particle production, as has been suggested for other human and insect viral genes. Suppression of chemotherapeutic drug induced cell death by bcl-2 and BHRF1, as demonstrated in this cell system, results in resistance to a variety of different agents and may represent an alternative mechanism by which multidrug resistance arises during chemotherapy.

Keywords

Programme Cell Death Epstein Barr Virus African Swine Fever African Swine Fever Virus Apoptotic Morphology 
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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • N. J. McCarthy
    • 1
    • 2
  • S. A. Hazlewood
    • 1
    • 3
  • D. S. Huen
    • 3
  • A. B. Rickinson
    • 3
  • G. T. Williams
    • 1
    • 2
  1. 1.Department of Biological SciencesKeele UniversityKeele, StaffordshireUK
  2. 2.Department of AnatomyUK
  3. 3.CRC Laboratories, Department of Cancer StudiesUniversity of Birmingham Medical SchoolBirminghamUK

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