Department of Medical Microbiology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, China.
Virus Res. 2012 Jun;166(1-2):23-30. doi: 10.1016/j.virusres.2012.02.022. Epub 2012 Mar 1.
The Epstein-Barr virus (EBV) BamHI-A rightward frame 1 (BARF1) gene is frequently expressed in EBV-associated epithelial malignancies and involves in oncogenicity and immunomodulation. To characterize the variations of BARF1 gene in different populations, the sequences of BARF1 gene in Northern Chinese nasopharyngeal carcinoma (NPC), EBV-associated gastric carcinoma (EBVaGC) and healthy donors were analyzed. The correlation of BARF1 variation with polymorphisms of BamHI F fragment (type F and f variants) and EBV-coded viral interleukin-10 (vIL-10) gene (B95-8 and SPM patterns) was also explored. Two major subtypes of BARF1 gene, designated as B95-8 and V29A, were identified. B95-8 subtype had identical amino acid sequence to B95-8 and was the dominant subtype among the EBV isolates from Northern China. V29A subtype, with one consistent amino acid change at residue 29 (V→A) and several nucleotide changes, showed higher frequency in NPC cases (25.3%, 20/79) than in EBVaGC cases (0/45) or healthy donors (4.3%, 2/46) (NPC vs. EBVaGC: P=0.0001; NPC vs. healthy donor: P=0.004). A preferential linkage between BamHI F and BARF1/vIL-10 polymorphisms was found. Type f isolates was specially correlated with the V29A/SPM genotype in NPC isolates and type f/V29A/SPM was preferentially found in NPC. BARF1/c-fms homology domain, transforming domain and cytotoxic T lymphocyte (CTL) epitopes of BARF1 were highly conserved in most isolates, suggesting the important role of BARF1 in virus infection and the potential usefulness in EBV-targeting immunotherapy of EBV-associated tumors. The relatively higher prevalence of type f/V29A/SPM strains in NPC may also suggest the association between these variations in multiple viral genes and NPC.
EB 病毒（EBV）BamHI-A 右向框 1（BARF1）基因在 EBV 相关上皮性恶性肿瘤中常被表达，参与致瘤性和免疫调节。为了研究 BARF1 基因在不同人群中的变异情况，对来自中国北方鼻咽癌（NPC）、EBV 相关胃癌（EBVaGC）和健康供体的 BARF1 基因序列进行了分析。还探讨了 BARF1 变异与 BamHI F 片段多态性（F 型和 f 型变体）和 EBV 编码的病毒白细胞介素 10（vIL-10）基因（B95-8 和 SPM 模式）之间的关系。鉴定出 BARF1 基因的两种主要亚型，分别命名为 B95-8 和 V29A。B95-8 亚型与 B95-8 的氨基酸序列完全相同，是中国北方 EBV 分离株中的主要亚型。V29A 亚型在 29 位（V→A）有一个一致的氨基酸变化，并有几个核苷酸变化，在 NPC 病例中的频率（25.3%，20/79）高于 EBVaGC 病例（0/45）或健康供体（4.3%，2/46）（NPC 与 EBVaGC：P=0.0001；NPC 与健康供体：P=0.004）。发现 BamHI F 与 BARF1/vIL-10 多态性之间存在优先连锁关系。f 型分离株与 NPC 分离株中的 V29A/SPM 基因型特别相关，而 f/V29A/SPM 则优先存在于 NPC 中。BARF1/c-fms 同源结构域、转化结构域和 BARF1 的细胞毒性 T 淋巴细胞（CTL）表位在大多数分离株中高度保守，提示 BARF1 在病毒感染中的重要作用，以及在 EBV 相关肿瘤的 EBV 靶向免疫治疗中的潜在用途。在 NPC 中，f/V29A/SPM 株的相对较高流行率也可能提示这些多种病毒基因的变异与 NPC 之间的关系。
