title: The roles of endoplasmic reticulum overload response induced by HCV and NS4B protein in human hepatocyte viability and virus replication.
abstract: Hepatitis C virus (HCV) replication is associated with endoplasmic reticulum (ER) and its infection triggers ER stress. In response to ER stress, ER overload response (EOR) can be activated, which involves the release of Ca2+ from ER, production of reactive oxygen species (ROS) and activation of nuclear factor κB (NF-κB). We have previously reported that HCV NS4B expression activates NF-κB via EOR-Ca2+-ROS pathway. Here, we showed that NS4B expression and HCV infection activated cancer-related NF-κB signaling pathway and induced the expression of cancer-related NF-κB target genes via EOR-Ca2+-ROS pathway. Moreover, we found that HCV-activated EOR-Ca2+-ROS pathway had profound effects on host cell viability and HCV replication. HCV infection induced human hepatocyte death by EOR-Ca2+-ROS pathway, whereas activation of EOR-Ca2+-ROS-NF-κB pathway increased the cell viability. Meanwhile, EOR-Ca2+-ROS-NF-κB pathway inhibited acute HCV replication, which could alleviate the detrimental effect of HCV on cell viability and enhance chronic HCV infection. Together, our findings provide new insights into the functions of EOR-Ca2+-ROS-NF-κB pathway in natural HCV replication and pathogenesis.
authors: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors: Lingbao
authors: L
authors: Kong
authors: Department of Plant Pathology & Microbiology, Iowa State University, Ames, Iowa, United States of America.
authors: Shanshan
authors: S
authors: Li
authors: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors: Mingjie
authors: M
authors: Huang
authors: Jiangxi Province Center for Disease Control and Prevention, Nanchang, Jiangxi, China.
authors: Ying
authors: Y
authors: Xiong
authors: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors: Qinghua
authors: Q
authors: Zhang
authors: School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
authors: Li
authors: L
authors: Ye
authors: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Science, Wuhan, Hubei, China.
authors: Jing
authors: J
authors: Liu
authors: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors: Xiangdong
authors: X
authors: Zhu
authors: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors: Ruina
authors: R
authors: Sun
authors: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors: Yunli
authors: Y
authors: Guo
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D002472:Cell Transformation, Viral; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D051456:Gene Flow; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D016328:NF-kappa B; C080107:NS4B protein, flavivirus; D017382:Reactive Oxygen Species; D017361:Viral Nonstructural Proteins; D002118:Calcium