Oncotarget

Research Papers:

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

Lu Dai, Lihua Bai, Zhen Lin, Jing Qiao, Liang Yang, Erik K. Flemington, Jovanny Zabaleta and Zhiqiang Qin _

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Oncotarget. 2016; 7:47052-47060. https://doi.org/10.18632/oncotarget.9720

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Abstract

Lu Dai1,2,4,*, Lihua Bai2,*, Zhen Lin6, Jing Qiao5, Liang Yang7, Erik K. Flemington6, Jovanny Zabaleta8, Zhiqiang Qin1,2,3

1Department of Oncology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China

2Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China

3Departments of Microbiology/Immunology/Parasitology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, 70112, USA

4Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, 70112, USA

5Department of Pediatrics, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China

6Department of Pathology, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA, 70112, USA

7Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, 637551, Singapore

8Department of Pediatrics, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, 70112, USA

*These authors contributed equally to this work

Correspondence to:

Zhiqiang Qin, email: [email protected]

Keywords: KSHV, interferon, oral fibroblast, viral oncogenesis

Received: March 27, 2016     Accepted: May 20, 2016     Published: May 30, 2016

ABSTRACT

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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