Transcriptional profiling of Epstein-Barr virus (EBV) genes and host cellular genes in nasal NK/T-cell lymphoma and chronic active EBV infection.

Transcriptional profiling of Epstein-Barr virus (EBV) genes and host cellular genes in nasal NK/T-cell lymphoma and chronic active EBV infection.
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DOI:
10.1038/sj.bjc.6602968
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发表时间:
2006-02-27
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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鼻NK/T细胞淋巴瘤是一种侵袭性非霍奇金淋巴瘤(NHL)亚型,与EB病毒(EBV)密切相关。EBV感染的NK或T细胞的克隆性扩增也见于慢性活动性EBV(CAEBV)感染的患者中,这表明两种疾病可能共享EBV影响宿主细胞基因表达的部分相似机制。为了了解EBV相关NK/T细胞淋巴增生性疾病(LPD)的发病机制并设计新的治疗方法,我们采用了一种新的EBV DNA微阵列来比较EBV相关NK/T细胞LPD建立的6种细胞系中EBV的表达模式。我们发现,表达BZLF 1,编码立即早期基因产物Zta,在SNK/T细胞中表达,表达水平优先在CAEBV感染的细胞系中高。我们还利用人寡核苷酸DNA微阵列分析了宿主细胞基因的基因表达模式。我们鉴定了一组致病和临床相关的宿主细胞基因,包括TNFRSF 10 D、CDK 2、HSPCA、IL 12 A作为EBV相关NK/T细胞LPD的常见分子生物学特性,以及一组基因,如PDCD 4作为疾病进展的假定贡献者。本研究从病毒和宿主基因表达方面描述了一种新的方法,该方法可以在EBV相关的NK/T细胞LPD中识别新的治疗靶点。
Nasal NK/T-cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma (NHL) that is closely associated with Epstein–Barr virus (EBV). The clonal expansion of EBV-infected NK or T cells is also seen in patients with chronic active EBV (CAEBV) infection, suggesting that two diseases might share a partially similar mechanism by which EBV affects host cellular gene expression. To understand the pathogenesis of EBV-associated NK/T-cell lymphoproliferative disorders (LPD) and design new therapies, we employed a novel EBV DNA microarray to compare patterns of EBV expression in six cell lines established from EBV-associated NK/T-cell LPD. We found that expression of BZLF1, which encodes the immediate-early gene product Zta, was expressed in SNK/T cells and the expression levels were preferentially high in cell lines from CAEBV infection. We also analyzsd the gene expression patterns of host cellular genes using a human oligonucleotide DNA microarray. We identified a subset of pathogenically and clinically relevant host cellular genes, including TNFRSF10D, CDK2, HSPCA, IL12A as a common molecular biological properties of EBV-associated NK/T-cell LPD and a subset of genes, such as PDCD4 as a putative contributor for disease progression. This study describes a novel approach from the aspects of viral and host gene expression, which could identify novel therapeutic targets in EBV-associated NK/T-cell LPD.
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