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

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 microenvironmen...

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Main Authors: Dai, Lu, Bai, Lihua, Lin, Zhen, Qiao, Jing, Yang, Liang, Flemington, Erik K., Zabaleta, Jovanny, Qin, Zhiqiang
Other Authors: Singapore Centre for Environmental Life Sciences Engineering
Format: Journal Article
Language:English
Published: 2018
Subjects:
Online Access:https://hdl.handle.net/10356/89951
http://hdl.handle.net/10220/46447
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author Dai, Lu
Bai, Lihua
Lin, Zhen
Qiao, Jing
Yang, Liang
Flemington, Erik K.
Zabaleta, Jovanny
Qin, Zhiqiang
author2 Singapore Centre for Environmental Life Sciences Engineering
author_facet Singapore Centre for Environmental Life Sciences Engineering
Dai, Lu
Bai, Lihua
Lin, Zhen
Qiao, Jing
Yang, Liang
Flemington, Erik K.
Zabaleta, Jovanny
Qin, Zhiqiang
author_sort Dai, Lu
collection NTU
description 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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spelling ntu-10356/899512020-09-21T11:32:11Z Transcriptomic analysis of KSHV-infected primary oral fibroblasts: the role of interferon-induced genes in the latency of oncogenic virus Dai, Lu Bai, Lihua Lin, Zhen Qiao, Jing Yang, Liang Flemington, Erik K. Zabaleta, Jovanny Qin, Zhiqiang Singapore Centre for Environmental Life Sciences Engineering KSHV Interferon DRNTU::Science::Biological sciences 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. Published version 2018-10-26T05:19:32Z 2019-12-06T17:37:18Z 2018-10-26T05:19:32Z 2019-12-06T17:37:18Z 2016 Journal Article Dai, L., Bai, L., Lin, Z., Qiao, J., Yang, L., Flemington, E. K., . . . Qin, Z. (2016). Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus. Oncotarget, 7(30), 47052-47060. doi:10.18632/oncotarget.9720 https://hdl.handle.net/10356/89951 http://hdl.handle.net/10220/46447 10.18632/oncotarget.9720 en Oncotarget © 2017 The Author(s) (published by Impact Journals). This paper is licensed under a Creative Commons Attribution 3.0 License. This paper was published in Oncotarget and is made available as an electronic reprint (preprint) with permission of The Author(s) (published by Impact Journals). The published version is available at: [http://dx.doi.org/10.18632/oncotarget.9720]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 9 p. application/pdf
spellingShingle KSHV
Interferon
DRNTU::Science::Biological sciences
Dai, Lu
Bai, Lihua
Lin, Zhen
Qiao, Jing
Yang, Liang
Flemington, Erik K.
Zabaleta, Jovanny
Qin, Zhiqiang
Transcriptomic analysis of KSHV-infected primary oral fibroblasts: the role of interferon-induced genes in the latency of oncogenic virus
title Transcriptomic analysis of KSHV-infected primary oral fibroblasts: the role of interferon-induced genes in the latency of oncogenic virus
title_full Transcriptomic analysis of KSHV-infected primary oral fibroblasts: the role of interferon-induced genes in the latency of oncogenic virus
title_fullStr Transcriptomic analysis of KSHV-infected primary oral fibroblasts: the role of interferon-induced genes in the latency of oncogenic virus
title_full_unstemmed Transcriptomic analysis of KSHV-infected primary oral fibroblasts: the role of interferon-induced genes in the latency of oncogenic virus
title_short Transcriptomic analysis of KSHV-infected primary oral fibroblasts: the role of interferon-induced genes in the latency of oncogenic virus
title_sort transcriptomic analysis of kshv infected primary oral fibroblasts the role of interferon induced genes in the latency of oncogenic virus
topic KSHV
Interferon
DRNTU::Science::Biological sciences
url https://hdl.handle.net/10356/89951
http://hdl.handle.net/10220/46447
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