Gan Yan-Jun, Razzouk Bassem I, Su Tao, Sixbey John W
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Am J Pathol. 2002 Mar;160(3):781-6. doi: 10.1016/S0002-9440(10)64900-0.
A ubiquitous herpesvirus that establishes life-long infection, the Epstein-Barr virus (EBV) has yielded little insight into how a single agent in general accord with its host can produce diverse pathologies ranging from oral hairy leukoplakia to nasopharyngeal carcinoma, from infectious mononucleosis to Hodgkin's disease (HD) and Burkitt's lymphoma. Its pathogenesis is further confounded by the less than total association of virus with histologically similar tumors. In other viral systems, defective (interfering) viral genomes are known to modulate outcome of infection, with either ameliorating or intensifying effects on disease processes initiated by prototype strains. To ascertain whether defective EBV genomes are present in HD, we examined paraffin-embedded tissue from 56 HD cases whose EBV status was first determined by cytohybridization for nonpolyadenylated EBV RNAs (EBERs). Using both standard polymerase chain reaction (PCR) and PCR in situ hybridization, we successfully amplified sequences that span abnormally juxtaposed BamHI W and Z fragments characteristic of defective heterogeneous (het) EBV DNA from 10 of 32 (31%) EBER-positive tumors. Of 24 EBER-negative HD, 8 yielded PCR products indicating presence of het EBV DNA. Two of these contained defective EBV in the apparent absence of the prototype virus. Of the 42 tumors analyzed for defective EBV by both PCR techniques, there was concordance of results in 38 (90%). Detection of defective EBV genomes with the potential to disrupt viral gene regulation suggests one mechanism for pathogenic diversity that may also account for loss of prototypic EBV from individual tumor cells.
爱泼斯坦-巴尔病毒（EBV）是一种普遍存在的疱疹病毒，可导致终身感染。然而，对于这样一种通常与宿主和谐共处的单一病原体，如何能引发从口腔毛状白斑到鼻咽癌、从传染性单核细胞增多症到霍奇金淋巴瘤（HD）和伯基特淋巴瘤等多种不同病变，我们却知之甚少。病毒与组织学上相似的肿瘤之间并非完全相关，这进一步混淆了其发病机制。在其他病毒系统中，已知缺陷（干扰）病毒基因组可调节感染结果，对原型毒株引发的疾病进程产生改善或加剧作用。为了确定HD中是否存在缺陷EBV基因组，我们检测了56例HD石蜡包埋组织，这些病例的EBV状态首先通过细胞杂交检测非多聚腺苷酸化EBV RNA（EBERs）来确定。使用标准聚合酶链反应（PCR）和PCR原位杂交技术，我们成功扩增出了跨越异常并列的BamHI W和Z片段的序列，这些片段是缺陷异质性（het）EBV DNA的特征，在32例（31%）EBER阳性肿瘤中的10例中检测到。在24例EBER阴性的HD中，8例产生了PCR产物，表明存在het EBV DNA。其中2例在明显没有原型病毒的情况下含有缺陷EBV。在通过两种PCR技术分析缺陷EBV的42个肿瘤中，38个（90%）结果一致。检测到具有破坏病毒基因调控潜力的缺陷EBV基因组，提示了一种致病多样性机制，这也可能解释了个别肿瘤细胞中原型EBV的缺失。
