Hepatitis C virus induces interferon-λ and interferon-stimulated genes in primary liver cultures.
Hepatitis C virus induces interferon-λ and interferon-stimulated genes in primary liver cultures.
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DOI：
10.1002/hep.24580
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发表时间：
2011-12
期刊：
影响因子：
13.5
通讯作者：
Dustin, Lynn B.
中科院分区：
文献类型：
--
作者：
Marukian, Svetlana;Andrus, Linda;Sheahan, Timothy P.;Jones, Christopher T.;Charles, Edgar D.;Ploss, Alexander;Rice, Charles M.;Dustin, Lynn B.
丙型肝炎病毒（HCV）在原代肝细胞中的复制不如肝癌细胞系中的强劲，这表明原代细胞中的先天抗病毒机制可能会限制HCV复制或传播。在这里，我们分析了来自 18 名不同供体的原代人胎儿肝细胞 (HFLC) 培养物的 HCV 感染后与干扰素 (IFN) 诱导和信号转导相关的 47 个基因的表达。我们报告细胞培养产生的 HCV (HCVcc) 诱导 III 型 (λ) IFN 和 IFN 刺激基因 (ISG) 的表达。检测到 I 型干扰素的表达很少。 IFNλ和ISG诱导水平在供体之间存在差异，并且通常在适应和非适应的HCV嵌合构建体之间存在差异。更高水平的病毒复制与更强的 ISG 和 λ IFN 诱导相关。基因诱导依赖于 HCV 复制，因为紫外线灭活的病毒不具有刺激性，而抗病毒药物 2'-C-甲基腺苷会减少 λ IFN 和 ISG 的诱导。诱导的IFNλ蛋白水平足以抑制初始培养物的HCVcc感染。总之，这些结果表明，尽管 HCV 感染据报道能够减弱 IFN 反应的诱导，但它能够在原代肝细胞培养物中诱导抗病毒细胞因子和途径。 ISG 和 λ IFN 的诱导可能会限制原代细胞培养物和受感染肝脏中 HCV 的生长和传播。 HCV感染HFLC可能为HCV体内基因诱导研究提供有用的模型。
Hepatitis C virus (HCV) replication in primary liver cells is less robust than that in hepatoma cell lines, suggesting that innate antiviral mechanisms in primary cells may limit HCV replication or spread. Here, we analyzed expression of 47 genes associated with interferon (IFN) induction and signaling following HCV infection of primary human fetal liver cell (HFLC) cultures from 18 different donors. We report that cell culture-produced HCV (HCVcc) induced expression of Type III (λ) IFNs and of IFN-stimulated genes (ISGs). Little expression of Type I IFNs was detected. Levels of IFNλ and ISG induction varied among donors and, often, between adapted and non-adapted HCV chimeric constructs. Higher levels of viral replication were associated with greater induction of ISGs and of λ IFNs. Gene induction was dependent on HCV replication, as UV-inactivated virus was not stimulatory and an antiviral drug, 2′-C-methyladenosine, reduced induction of λ IFNs and ISGs. The level of IFNλ protein induced was sufficient to inhibit HCVcc infection of naïve cultures. Together, these results indicate that despite its reported abilities to blunt the induction of an IFN response, HCV infection is capable of inducing antiviral cytokines and pathways in primary liver cell cultures. Induction of ISGs and λ IFNs may limit the growth and spread of HCV in primary cell cultures and in the infected liver. HCV infection of HFLC may provide a useful model for the study of gene induction by HCV in vivo.
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影响因子：
46.9
作者：
通讯作者：
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影响因子：
5.4
作者：
Bigger, CB;Guerra, B;Lanford, RE
通讯作者：
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影响因子：
64.8
作者：
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影响因子：
13.5
作者：
Major, ME;Dahari, H;Feinstone, SM
通讯作者：
Feinstone, SM
DOI：
10.1073/pnas.0408707102
发表时间：
2005-02-22
影响因子：
11.1
作者：
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通讯作者：
Gale, M