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[爱泼斯坦-巴尔病毒对伯基特淋巴瘤细胞系中宿主基因表达的影响]

[Effects of Epstein-Barr virus on host gene expression in Burkitt's lymphoma cell lines].

作者信息

Broderick Peter, Hubank Michael, Sinclair Alison

机构信息

School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom.

出版信息

Ai Zheng. 2009 Aug;28(8):813-21. doi: 10.5732/cjc.009.10061.

Abstract

BACKGROUND AND OBJECTIVE

Epstein-Barr virus (EBV) is present in Burkitt's lymphoma (BL) cells in a latent form, showing a highly restricted pattern of gene expression with few tumor cells undergoing viral lytic replication. BL cell lines can be induced to enter the viral lytic cycle and initiate replication by stimulating surface immunoglobulin molecules. During this process many EBV genes are expressed that have the potential to influence host gene expression. We aimed to identify host genes that are regulated by EBV in BL cells and those that are regulated following ligation of surface IgG.

METHODS

The differentially expressed genes in EBV-positive Akata cells and EBV-negative AK31 cells were detected by microarray.

RESULTS

A total of 91 human genes were differentially expressed between Akata and AK31 cells and 198 were differentially expressed when cells were stimulated to enter lytic replication. The differential expression of one gene, myd88, was correlated with disrupted TLR9 signaling.

CONCLUSIONS

EBV down-regulates most of the genes regulated by surface Ig cross-linking in the early stages of lytic cycle activation. These include genes involved in cell survival, signal transduction, transcription control and the immune response that may mediate EBV transformation of B-lymphocytes and others such as HDAC4 that may affect virus replication.

摘要

背景与目的

爱泼斯坦-巴尔病毒(EBV)以潜伏形式存在于伯基特淋巴瘤(BL)细胞中,呈现出高度受限的基因表达模式,仅有少数肿瘤细胞进行病毒裂解复制。BL细胞系可通过刺激表面免疫球蛋白分子被诱导进入病毒裂解周期并启动复制。在此过程中,许多EBV基因得以表达,这些基因有可能影响宿主基因表达。我们旨在鉴定在BL细胞中受EBV调控的宿主基因以及在表面IgG连接后受调控的基因。

方法

通过微阵列检测EBV阳性的Akata细胞和EBV阴性的AK31细胞中差异表达的基因。

结果

Akata细胞和AK31细胞之间共有91个人类基因差异表达,当细胞被刺激进入裂解复制时,有198个基因差异表达。一个基因myd88的差异表达与TLR9信号传导中断相关。

结论

在裂解周期激活的早期阶段,EBV下调了大多数受表面Ig交联调控的基因。这些基因包括参与细胞存活、信号转导、转录控制和免疫反应的基因,它们可能介导EBV对B淋巴细胞的转化,以及其他可能影响病毒复制的基因,如HDAC4。

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