Identification of an Epstein-Barr virus early gene encoding a second component of the restricted early antigen complex

Long-Term MHC Class II Presentation of the EBV Lytic Protein BHRF1 by EBV Latently Infected B Cells following Capture of BHRF1 Antigen

“…Expression of BHRF1 during latency has been suggested in the past, because differentially spliced BHRF1-containing mRNAs were detected by Northern blot analysis in latently infected LCLs (35) and in EBVassociated B cell lymphomas (36). However, Kieff et al (37) reported that neither BHRF1 mRNA nor BHRF1 protein could be detected in latently infected cells. Staining of various LCL cell lines with a BHRF1-specific mAb was shown to be restricted to a few cells, corresponding to those undergoing a lytic cycle (38), and BHRF1 could not be detected in post-transplantation lymphoproliferative disorders (39).…”

Laying the foundations of programmed cell death

“…After BCL-2 was cloned and initially characterized, subsequent work by other laboratories identified other key mammalian relatives, including BCL-X L , 9 MCL-1, 10 BFL-1, 11 and BCL-w. 12 Important viral homologues were also identified, including E1B 19K protein in adenovirus, 13 BHRF-1 in Epstein-Barr virus, 14 and a BCL-2 homolog in Kaposi sarcoma herpes virus. 15 A major paradigm shift occurred with the identification of the first proapoptotic interacting relative of BCL-2, BAX, in Stan's laboratory.…”

In memoriam of a prominent composer of the Bcl-2 family symphony

“…This indicated that Bcl-2 was not the only member of its kind to regulate apoptosis during embryonic development and tissue/ cell turnover. In 1987, Pearson et al 13 already discovered that the BHRF1 protein from Epstein-Barr virus had extensive sequence homology to Bcl-2 and proposed that the virus could use this potentially antiapoptotic protein to sustain the survival of host cells during progeny production (for an update on viral homologues, see reviews by Marie Hardwick and Eileen White). However, it was not yet clear if additional homologues of Bcl-2 were needed for apoptosis regulation in mammals.…”

“…Do we know today? Well, for almost a decade we Cell Death and Differentiation (2006) 13,[1248][1249] have been arguing at each apoptosis conference and in numerous reviews (including in the present series) whether some BH3 only proteins (such as Bim, Bid or Puma) directly activate Bax and Bak by a kiss-and-run-away paradigm or whether all these proteins are in high-affinity love with Bcl-2 survival factors 20 and as a consequence chase off Baxand Bak-, or some Bax/Bak-activating factors, which were previously bound. Stan would have liked to enter into this sort of discussion as his group was among those who proposed 'activator' (directly acting on Bax/Bak) and 'derepressor' (acting via Bcl-2-like factors) subspecies of BH3-only proteins 21 (for further discussions on this subject, see the reviews by David Huang and Andreas Villunger, in this issue).…”