Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus.

Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus.
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KSHV 感染的原代口腔成纤维细胞的转录组分析:干扰素诱导基因在致癌病毒潜伏期中的作用

DOI:
10.18632/oncotarget.9720
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发表时间:
2016-07-26
期刊:
影响因子:
--
通讯作者:
Qin Z
Qin Z
中科院分区:
其他
文献类型:
--
作者:
Dai L;Bai L;Lin Z;Qiao J;Yang L;Flemington EK;Zabaleta J;Qin Z

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卡波西肉瘤相关疱疹病毒(KSHV)是卡波西肉瘤(KS)的病原体,KS是世界上最常见的HIV/ aids相关肿瘤。累及口腔预示着KS患者预后不良,但KSHV调节口腔肿瘤微环境的机制在很大程度上是未知的。在KS病变中发现浸润性成纤维细胞,KSHV可以在体外和体内的人原代成纤维细胞中建立潜伏感染,但KSHV感染的成纤维细胞对KS微环境的贡献此前尚未被描述。在本研究中,我们使用Illumina芯片检测了kshv感染的原代人口腔成纤维细胞(PDLF和HGF)的整体基因表达变化。在显著改变的候选细胞中,我们发现在这些kshv感染的口腔细胞中,一系列干扰素诱导的基因被强烈上调。有趣的是,其中一些基因,特别是ISG15和ISG20,是通过调节特定的KSHV microrna来维持病毒潜伏期所必需的。我们的数据表明,口腔成纤维细胞可能代表了一种重要的宿主细胞防御病毒感染的成分,以及作为疱疹病毒在口腔终身感染的储存库。
The Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Involvement of the oral cavity portends a poor prognosis for patients with KS, but the mechanisms for KSHV regulation of the oral tumor microenvironment are largely unknown. Infiltrating fibroblasts are found within KS lesions, and KSHV can establish latent infection within human primary fibroblasts in vitro and in vivo, but contributions for KSHV-infected fibroblasts to the KS microenvironment have not been previously characterized. In the present study, we used Illumina microarray to determine global gene expression changes in KSHV-infected primary human oral fibroblasts (PDLF and HGF). Among significantly altered candidates, we found that a series of interferon-induced genes were strongly up-regulated in these KSHV-infected oral cells. Interestingly, some of these genes in particular ISG15 and ISG20 are required for maintenance of virus latency through regulation of specific KSHV microRNAs. Our data indicate that oral fibroblasts may represent one important host cellular defense component against viral infection, as well as acting as a reservoir for herpesvirus lifelong infection in the oral cavity.
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