BHRF1 is highly conserved in primate virus analogues of Epstein-Barr virus

The Epstein-Barr virus (EBV) protein BHRF1 (BamHI rightward reading frame 1) was the first viral member of the Bcl-2 family of apoptosis-regulating proteins described. In vitro studies imply that BHRF1 is dispensable for virus-induced cellular transformation and virus replication. However, in contrast to several essential viral genes that show divergence outwith their functional domains, sequence data from a wide range of EBV isolates show there is striking conservation of the BHRF1 gene. Contrary to the in vitro studies, the high degree of conservation hints at a more important role for BHRF1. Analogous viruses are endemic in each of the higher primate species. Whilst their genome organisation is colinear, limited sequence analysis indicates that the viruses have diverged significantly and that only important functional domains of proteins are likely to be conserved. We have isolated the BHRF1 equivalents from the viruses which infect chimpanzees (Herpesvirus pan) and baboons (Herpesvirus papio) and find that they are highly homologous in both species, strengthening the hypothesis that BHRF1 plays a significant, evolutionarily conserved function in vivo and that changes to the protein are not well tolerated.