Khanim F, Dawson C, Meseda C A, Dawson J, Mackett M, Young L S
CRC Institute for Cancer Studies, The University of Birmingham Medical School, UK.
J Gen Virol. 1997 Nov;78 ( Pt 11):2987-99. doi: 10.1099/0022-1317-78-11-2987.
BHRF 1, a component of the restricted early antigen (EA) complex of the Epstein-Barr virus (EBV) lytic cycle, encodes a 17 kDa putative transmembrane protein with both sequence and functional homology to the Bcl-2 proto-oncogene. To determine whether there was any sequence variation over the BHRF1 open reading frame (ORF), 15 EBV isolates from different geographical regions and from both healthy donors and patients with EBV-associated diseases were sequenced. A small number of base changes which resulted in amino acid substitutions in the BHRF1 protein were found relative to the prototype B95.8 EBV sequence and these were predominantly clustered near the amino terminus of the BHRF1 protein outside conserved domains identified in the Bcl-2 homologues. In transient transfection assays none of the mutations in the BHRF1 ORF from eight different EBV isolates had a significant effect on BHRF1 protein localization compared to the B95.8 BHRF1 protein. However, transient expression of the adenovirus 12 19K protein or Bcl-2 resulted in localization patterns distinct from that observed with BHRF1 protein. Whilst all eight EBV isolates and E1B-19K gave comparable levels of protection to the DNA-damaging agent cis-platin, Bcl-2 did not afford significant protection. Thus, despite several amino acid changes in the BHRF1 ORF of some of the EBV isolates studied, the ability of the protein to protect against cis-platin induced apoptosis is conserved. The highly conserved nature of BHRF1 amongst different EBV isolates at both the sequence and functional level supports the proposed important role of BHRF1 in delaying cell death, thereby maximizing the production of progeny virus and facilitating the establishment of virus persistence.
BHRF1是爱泼斯坦-巴尔病毒（EBV）裂解周期中受限早期抗原（EA）复合物的一个组成部分，编码一种17 kDa的推定跨膜蛋白，与Bcl-2原癌基因在序列和功能上具有同源性。为了确定BHRF1开放阅读框（ORF）上是否存在任何序列变异，对来自不同地理区域、健康供体以及EBV相关疾病患者的15株EBV分离株进行了测序。相对于原型B95.8 EBV序列，发现了少量导致BHRF1蛋白氨基酸替换的碱基变化，这些变化主要聚集在BHRF1蛋白氨基末端附近，位于Bcl-2同源物中确定的保守结构域之外。在瞬时转染试验中，与B95.8 BHRF1蛋白相比，来自8种不同EBV分离株的BHRF1 ORF中的突变均未对BHRF1蛋白定位产生显著影响。然而，腺病毒12 19K蛋白或Bcl-2的瞬时表达导致的定位模式与BHRF1蛋白观察到的不同。虽然所有8株EBV分离株和E1B-19K对DNA损伤剂顺铂提供了相当水平的保护，但Bcl-2并未提供显著保护。因此，尽管在所研究的一些EBV分离株的BHRF1 ORF中有几个氨基酸变化，但该蛋白抵御顺铂诱导凋亡的能力是保守的。BHRF1在不同EBV分离株中在序列和功能水平上的高度保守性质支持了BHRF1在延迟细胞死亡中所起的重要作用，从而使子代病毒产量最大化并促进病毒持续性的建立。
