Sample J, Young L, Martin B, Chatman T, Kieff E, Rickinson A, Kieff E
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
J Virol. 1990 Sep;64(9):4084-92. doi: 10.1128/JVI.64.9.4084-4092.1990.
The two Epstein-Barr virus (EBV) types, EBV-1 and EBV-2, are known to differ in their EBNA-2 genes, which are 64 and 53% identical in their nucleotide and predicted amino acid sequences, respectively. Restriction endonuclease maps and serologic analyses detect few other differences between EBV-1 and EBV-2 except in the EBNA-3 gene family. We determined the DNA sequence of the AG876 EBV-2 EBNA-3 coding region and have compared it with known B95-8 EBV-1 EBNA-3 sequences to delineate the extent of divergence between EBV-1 and EBV-2 isolates in their EBNA-3 genes. The B95-8 and AG876 EBV isolates had nucleotide and amino acid identity levels of 90 and 84%, 88 and 80%, and 81 and 72% for the EBNA-3A, -3B, and -3C genes, respectively. In contrast, nucleotide sequence identity in the noncoding DNA adjacent to the B95-8 and AG876 EBNA-3 open reading frames was 96%. We used the polymerase chain reaction to demonstrate that five additional EBV-1 isolates and six additional EBV-2 isolates have the type-specific differences in their EBNA-3 genes predicted from the B95-8 or AG876 sequences. Thus, EBV-1 and EBV-2 are two distinct wild-type EBV strains that have significantly diverged at four genetic loci and have maintained type-characteristic differences at each locus. The delineation of these sequence differences between EBV-1 and EBV-2 is essential to ongoing molecular dissection of the biologic properties of EBV and of the human immune response to EBV infection. The application of these data to the delineation of epitopes recognized in the EBV-immune T-cell response is also discussed.
已知两种爱泼斯坦-巴尔病毒（EBV）类型，即EBV-1和EBV-2，在其EBNA-2基因上存在差异，这两个基因的核苷酸序列和预测的氨基酸序列分别有64%和53%的同源性。除了EBNA-3基因家族外，限制性内切酶图谱和血清学分析几乎未检测到EBV-1和EBV-2之间的其他差异。我们测定了AG876 EBV-2 EBNA-3编码区的DNA序列，并将其与已知的B95-8 EBV-1 EBNA-3序列进行比较，以确定EBV-1和EBV-2分离株在其EBNA-3基因上的差异程度。B95-8和AG876 EBV分离株的EBNA-3A、-3B和-3C基因的核苷酸和氨基酸同源性水平分别为90%和84%、88%和80%、81%和72%。相比之下，与B95-8和AG876 EBNA-3开放阅读框相邻的非编码DNA中的核苷酸序列同源性为96%。我们使用聚合酶链反应证明，另外5个EBV-1分离株和6个EBV-2分离株在其EBNA-3基因中具有从B95-8或AG876序列预测的类型特异性差异。因此，EBV-1和EBV-2是两种不同的野生型EBV毒株，它们在四个基因位点上有显著差异，并且在每个位点上都保持着类型特征性差异。确定EBV-1和EBV-2之间的这些序列差异对于正在进行的EBV生物学特性和人类对EBV感染的免疫反应的分子剖析至关重要。本文还讨论了这些数据在确定EBV免疫T细胞反应中识别的表位方面的应用。
