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Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway

BACKGROUND: Hepatitis C virus (HCV) is the leading cause of liver fibrosis, cirrhosis and hepatocellular carcinoma. It is believed that continuous liver cell apoptosis contributes to HCV pathogenesis. Recent studies have shown that HCV infection can sensitize host cells to TNF-related apoptosis-indu...

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Autores principales: Deng, Zhongfan, Yan, Huijuan, Hu, Jiajie, Zhang, Shengwei, Peng, Peng, Liu, Qingzhen, Guo, Deyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360765/
https://www.ncbi.nlm.nih.gov/pubmed/22662193
http://dx.doi.org/10.1371/journal.pone.0037700
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author Deng, Zhongfan
Yan, Huijuan
Hu, Jiajie
Zhang, Shengwei
Peng, Peng
Liu, Qingzhen
Guo, Deyin
author_facet Deng, Zhongfan
Yan, Huijuan
Hu, Jiajie
Zhang, Shengwei
Peng, Peng
Liu, Qingzhen
Guo, Deyin
author_sort Deng, Zhongfan
collection PubMed
description BACKGROUND: Hepatitis C virus (HCV) is the leading cause of liver fibrosis, cirrhosis and hepatocellular carcinoma. It is believed that continuous liver cell apoptosis contributes to HCV pathogenesis. Recent studies have shown that HCV infection can sensitize host cells to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis, but the mechanism by which HCV regulates the TRAIL pathway remains unclear. METHODS AND RESULTS: Using a sub-genomic replicon and full length virus, JFH-1, we demonstrate that HCV can sensitize host cells to TRAIL-induced apoptosis by up-regulating two TRAIL receptors, death receptor 4 (DR4) and death receptor 5 (DR5). Furthermore, the HCV replicon enhanced transcription of DR5 via Sp1, and the HCV-mediated up-regulation of DR4 and DR5 required MEK1 activity. HCV infection also stimulated the activity of MEK1, and the inhibition of MEK1 activity or the knockdown of MEK1 increased the replication of HCV. CONCLUSIONS: Our studies demonstrate that HCV replication sensitizes host cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5 via a MEK1 dependent pathway. These findings may help to further understand the pathogenesis of HCV infection and provide a therapeutic target.
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spelling pubmed-33607652012-06-01 Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway Deng, Zhongfan Yan, Huijuan Hu, Jiajie Zhang, Shengwei Peng, Peng Liu, Qingzhen Guo, Deyin PLoS One Research Article BACKGROUND: Hepatitis C virus (HCV) is the leading cause of liver fibrosis, cirrhosis and hepatocellular carcinoma. It is believed that continuous liver cell apoptosis contributes to HCV pathogenesis. Recent studies have shown that HCV infection can sensitize host cells to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis, but the mechanism by which HCV regulates the TRAIL pathway remains unclear. METHODS AND RESULTS: Using a sub-genomic replicon and full length virus, JFH-1, we demonstrate that HCV can sensitize host cells to TRAIL-induced apoptosis by up-regulating two TRAIL receptors, death receptor 4 (DR4) and death receptor 5 (DR5). Furthermore, the HCV replicon enhanced transcription of DR5 via Sp1, and the HCV-mediated up-regulation of DR4 and DR5 required MEK1 activity. HCV infection also stimulated the activity of MEK1, and the inhibition of MEK1 activity or the knockdown of MEK1 increased the replication of HCV. CONCLUSIONS: Our studies demonstrate that HCV replication sensitizes host cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5 via a MEK1 dependent pathway. These findings may help to further understand the pathogenesis of HCV infection and provide a therapeutic target. Public Library of Science 2012-05-25 /pmc/articles/PMC3360765/ /pubmed/22662193 http://dx.doi.org/10.1371/journal.pone.0037700 Text en Deng et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Deng, Zhongfan
Yan, Huijuan
Hu, Jiajie
Zhang, Shengwei
Peng, Peng
Liu, Qingzhen
Guo, Deyin
Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway
title Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway
title_full Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway
title_fullStr Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway
title_full_unstemmed Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway
title_short Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway
title_sort hepatitis c virus sensitizes host cells to trail-induced apoptosis by up-regulating dr4 and dr5 via a mek1-dependent pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360765/
https://www.ncbi.nlm.nih.gov/pubmed/22662193
http://dx.doi.org/10.1371/journal.pone.0037700
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