Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation

Abstract The life cycle of hepatitis C virus (HCV) is highly dependent on host proteins for virus propagation. By transcriptome sequencing analysis, we identified host genes that were highly differentially expressed in HCV-infected cells. Of these candidates, we selected Death receptor 6 (DR6) for f...

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Autores principales:	Trang T. D. Luong, Giao V. Q. Tran, Dong-Jo Shin, Yun-Sook Lim, Soon B. Hwang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9de472c49b474a6891d23ce602b6f2f4
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spelling	oai:doaj.org-article:9de472c49b474a6891d23ce602b6f2f42021-12-02T12:32:58ZHepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation10.1038/s41598-017-06740-92045-2322https://doaj.org/article/9de472c49b474a6891d23ce602b6f2f42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06740-9https://doaj.org/toc/2045-2322Abstract The life cycle of hepatitis C virus (HCV) is highly dependent on host proteins for virus propagation. By transcriptome sequencing analysis, we identified host genes that were highly differentially expressed in HCV-infected cells. Of these candidates, we selected Death receptor 6 (DR6) for further characterization. DR6 is an orphan member of the tumor necrosis factor receptor superfamily. In the present study, we demonstrated that both mRNA and protein levels of DR6 were increased in the context of HCV replication. We further showed that promoter activity of DR6 was increased by HCV infection. By employing promoter-linked reporter assay, we showed that HCV upregulated DR6 via ROS-mediated NF-κB pathway. Both mRNA and protein levels of DR6 were increased by NS4B or NS5A. However, NS5A but not NS4B specifically interacted with DR6. We showed that HCV modulated JNK, p38 MAPK, STAT3, and Akt signaling pathways in a DR6-dependent manner. Interestingly, Akt signaling cascade was regulated by protein interplay between DR6 and NS5A. Silencing of DR6 expression resulted in decrease of infectious HCV production without affecting viral entry, replication, and translation. Together, these data indicate that HCV modulates DR6 signaling pathway for viral propagation and may contribute to HCV-mediated pathogenesis.Trang T. D. LuongGiao V. Q. TranDong-Jo ShinYun-Sook LimSoon B. HwangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Trang T. D. Luong Giao V. Q. Tran Dong-Jo Shin Yun-Sook Lim Soon B. Hwang Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation
description	Abstract The life cycle of hepatitis C virus (HCV) is highly dependent on host proteins for virus propagation. By transcriptome sequencing analysis, we identified host genes that were highly differentially expressed in HCV-infected cells. Of these candidates, we selected Death receptor 6 (DR6) for further characterization. DR6 is an orphan member of the tumor necrosis factor receptor superfamily. In the present study, we demonstrated that both mRNA and protein levels of DR6 were increased in the context of HCV replication. We further showed that promoter activity of DR6 was increased by HCV infection. By employing promoter-linked reporter assay, we showed that HCV upregulated DR6 via ROS-mediated NF-κB pathway. Both mRNA and protein levels of DR6 were increased by NS4B or NS5A. However, NS5A but not NS4B specifically interacted with DR6. We showed that HCV modulated JNK, p38 MAPK, STAT3, and Akt signaling pathways in a DR6-dependent manner. Interestingly, Akt signaling cascade was regulated by protein interplay between DR6 and NS5A. Silencing of DR6 expression resulted in decrease of infectious HCV production without affecting viral entry, replication, and translation. Together, these data indicate that HCV modulates DR6 signaling pathway for viral propagation and may contribute to HCV-mediated pathogenesis.
format	article
author	Trang T. D. Luong Giao V. Q. Tran Dong-Jo Shin Yun-Sook Lim Soon B. Hwang
author_facet	Trang T. D. Luong Giao V. Q. Tran Dong-Jo Shin Yun-Sook Lim Soon B. Hwang
author_sort	Trang T. D. Luong
title	Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation
title_short	Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation
title_full	Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation
title_fullStr	Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation
title_full_unstemmed	Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation
title_sort	hepatitis c virus exploits death receptor 6-mediated signaling pathway to facilitate viral propagation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9de472c49b474a6891d23ce602b6f2f4
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Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation

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