Epstein-Barr Virus BHRF1 Protein Protects against Cell Death Induced by DNA-Damaging Agents and Heterologous Viral Infection

Viruses with deletions in antiapoptotic genes as potential oncolytic agents

“…Virus encoded Bcl-2 homologs have also been reported for g-1 herpes virus (EBV) and g-2 herpes virus (HHV-8 and herpesvirus saimiri) (Tarodi et al, 1994;Cheng et al, 1997;Nava et al, 1997). However, there is no report on v-Bcl-2 in a herpes virus (HSV-1) or other viral species being used for oncolytic purposes.…”

Functional dissection of Bfl-1, a Bcl-2 homolog: anti-apoptosis, oncogene-cooperation and cell proliferation activities

“…The cellular proteins of the BCL-2 family with antiapoptosis activity include BCL-2 (Korsmeyer, 1992;Reed, 1994), BCL-x L (Boise et al, 1993), MCL-1 (Reynolds et al, 1994), NR-13 (Mangeney et al, 1996) and BFL-1 (D' Sa-Eipper et al, 1996). Several viral homologs such as Epstein Barr virus-BHRF1 (Henderson et al, 1993;Takayama et al, 1994;Tarodi et al, 1994), adenovirus E1B-19kDa Tarodi et al, 1993), KSBCL-2/ORF 16 of HHV-8 (Russo et al, 1996;Cheng et al, 1997) and Herpes virus saimiri ORF 16 (Smith, 1995;Nava et al, 1997) also promote cell survival. In contrast, several BCL-2 family members which share one or more conserved domains, promote cell death.…”

BHRF1, a viral homologue of the Bcl-2 oncogene, is conserved at both the sequence and functional level in different Epstein-Barr virus isolates.

“…Although dispensable for both virus-induced cell growth transformation in vitro and virus replication (Marchini et al, 1991 ;Lee & Yates, 1992), BHRF1 has a proven ability to act as a cell survival gene. EBV-negative BL cells expressing BHRF1 are rendered more resistant to programmed cell death (apoptosis) under experimental conditions of growth factor withdrawal and rodent hamster fibroblasts expressing BHRF1 display increased resistance to the apoptotic inducing effects of DNA-damaging drugs (Henderson et al, 1993 ;Tarodi et al, 1994). These studies suggest that whilst BHRF1 is not consistently expressed in F. Khanim and others F. Khanim and others EBV-associated tumours, it is possible that expression of this protein at an early stage in the oncogenic process may influence the development of these malignancies.…”