Kanegane H, Wang F, Tosato G
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
Blood. 1996 Dec 15;88(12):4667-75.
Lymphoproliferative disorders involving Epstein-Barr virus (EBV) infected natural killer (NK) cells are reported with increasing frequency, but the nature and role of EBV infection in these cells remains undefined. In this study, we have investigated virus-cell interactions in the EBV-positive YTN10 cell line, an NK-like cell line established from a patient with lymphoblastic lymphoma. Low level expression of the EBV receptor CD21 molecule was detected by FACS and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Immunoblotting and RT-PCR analysis identified a latency II pattern of EBV gene expression, consisting of EBNA-1 transcription from the Qp promoter, in the absence of other EBNA gene expression, and accompanied by LMP-1 and LMP-2A expression. The EBV genome was present in episomal form and there was evidence for lytic viral replication. This latency pattern is typical of EBV gene expression in nasopharyngeal carcinoma and Hodgkin's disease, and differs from the full spectrum of EBV latent gene expression in most posttransplant lymphoproliferative disorders and from the restricted EBNA-1 expression in Burkitt's lymphoma tissues. The interaction between EBV and NK cells described here has important implications for the pathogenesis and treatment of EBV-infected NK malignancies.
涉及爱泼斯坦-巴尔病毒(EBV)感染的自然杀伤(NK)细胞的淋巴增殖性疾病报告频率日益增加,但EBV感染在这些细胞中的性质和作用仍不明确。在本研究中,我们调查了EBV阳性的YTN10细胞系中的病毒-细胞相互作用,该细胞系是从一名淋巴细胞淋巴瘤患者建立的NK样细胞系。通过荧光激活细胞分选术(FACS)和逆转录聚合酶链反应(RT-PCR)分析检测到EBV受体CD21分子的低水平表达。免疫印迹和RT-PCR分析确定了EBV基因表达的潜伏期II模式,即在没有其他EBNA基因表达的情况下,由Qp启动子转录的EBNA-1,并伴有LMP-1和LMP-2A表达。EBV基因组以附加体形式存在,并有溶细胞性病毒复制的证据。这种潜伏期模式是EBV在鼻咽癌和霍奇金病中基因表达的典型特征,与大多数移植后淋巴增殖性疾病中EBV潜伏基因表达的全谱不同,也与伯基特淋巴瘤组织中受限的EBNA-1表达不同。本文所述的EBV与NK细胞之间的相互作用对EBV感染的NK恶性肿瘤的发病机制和治疗具有重要意义。