Dai Lu, Bai Lihua, Lin Zhen, Qiao Jing, Yang Liang, Flemington Erik K, Zabaleta Jovanny, Qin Zhiqiang
Department of Oncology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Oncotarget. 2016 Jul 26;7(30):47052-47060. doi: 10.18632/oncotarget.9720.
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.
卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤（KS）的病原体，KS是全球最常见的与艾滋病相关的肿瘤。口腔受累预示着KS患者预后不良，但KSHV调节口腔肿瘤微环境的机制尚不清楚。在KS病变中发现有浸润的成纤维细胞，KSHV在体外和体内均可在人原代成纤维细胞中建立潜伏感染，但此前尚未明确KSHV感染的成纤维细胞对KS微环境的作用。在本研究中，我们使用Illumina微阵列来确定KSHV感染的原代人口腔成纤维细胞（PDLF和HGF）中的全局基因表达变化。在显著改变的候选基因中，我们发现一系列干扰素诱导基因在这些KSHV感染的口腔细胞中强烈上调。有趣的是，其中一些基因，特别是ISG15和ISG20，通过调节特定的KSHV微小RNA来维持病毒潜伏。我们的数据表明，口腔成纤维细胞可能是宿主对抗病毒感染的一种重要细胞防御成分，同时也作为疱疹病毒在口腔终身感染的储存库。
