Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector
Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector
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DOI：
10.1002/hep.20844
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发表时间：
2005-09-01
期刊：
影响因子：
13.5
通讯作者：
Beard, MR
中科院分区：
文献类型：
--
作者：
Helbig, KJ;Lau, DTY;Beard, MR
干扰素(IFN) α在临床和体外抑制丙型肝炎病毒（HCV）复制然而，在HCV感染的肝脏中表达的干扰素刺激基因（ISGs）的完整谱或负责控制HCV复制的基因尚未确定。为了更好地确定ISG在慢性丙型肝炎病毒感染肝脏中的表达，对9例慢性丙型肝炎（CHC）患者进行了DNA芯片分析。其中很大一部分是转录升高的潜在isg，表明对内源性IFN和/或双链RNA的持续反应。所有患者中有一种ISG显著升高是viperin，这是一种进化保守的ISG，对人巨细胞病毒具有抗病毒活性。用ifn - α或- γ刺激Huh-7和HepG2细胞显示viperin主要是I型ISG。此外，用poly（I:Q）或HCV RNA转染Huh-7细胞也可以诱导viperin的表达。在含有HCV基因组复制子的细胞中短暂表达viperin导致HCV复制显著减少，这表明viperin具有抗HCV活性。总之，即使面对持续的HCV感染，也存在活跃的ISG抗病毒细胞反应，突出了宿主病毒关系的复杂性。此外，ISG蝰蛇素在体外具有抗hcv活性；我们假设viperin和其他isg一起限制了HCV的复制。
Interferon (IFN) alpha inhibits hepatitis C virus (HCV) replication both clinically and in vitro; however, the complete spectrum of interferon-stimulated genes (ISGs) expressed in the HCV-infected liver or the genes responsible for control of HCV replication have not been defined. To better define ISG expression in the chronically infected HCV liver, DNA microarray analysis was performed on 9 individuals with chronic hepatitis C (CHC). A total of 232 messenger RNAs were differentially regulated in CHC compared with nondiseased liver controls. A significant proportion of these were potential ISGs that were transcriptionally elevated, suggesting an ongoing response to endogenous IFN and/or double-stranded RNA. One ISG significantly elevated in all patients was viperin, an evolutionary conserved ISG that has antiviral activity against human cytomegalovirus. Stimulation of Huh-7 and HepG2 cells with IFN-alpha or -gamma revealed viperin is predominantly a type I ISG. Furthermore, viperin expression could also be induced following transfection of Huh-7 cells with either poly(I:Q or HCV RNA. Transient expression of viperin in cells harboring the HCV genomic replicon resulted in a significant decrease in HCV replication, suggesting that viperin has anti-HCV activity. In conclusion, even in the face of a persistent HCV infection, there is an active ISG antiviral cellular response, highlighting the complexity of the host viral relationship. Furthermore, ISG viperin has anti-HCV activity in vitro; we postulate that viperin, along with other ISGs, acts to limit HCV replication.