HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection.
HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection.
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DOI：
10.1002/hep.27227
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发表时间：
2014-10
期刊：
影响因子：
13.5
通讯作者：
Evans, Matthew J.
中科院分区：
文献类型：
--
作者：
Israelow, Benjamin;Narbus, Christopher M.;Sourisseau, Marion;Evans, Matthew J.
丙型肝炎病毒（HCV）暴露导致持续的终身感染，其特征是慢性炎症，通常发展为肝硬化和肝细胞癌。丙型肝炎病毒在肝脏中残留，同时诱导炎症和抗病毒反应的机制尚不清楚。虽然患者对HCV的先天免疫应答似乎相当活跃，但已在细胞培养中显示HCV采用多种先天免疫拮抗剂，这表明目前研究HCV与先天免疫系统之间相互作用的模型系统不能代表体内发生的情况。我们最近发现，如果肝脏特异性microRNA miR-122与进入因子CD 81一起沿着表达，则肝癌衍生的HepG 2细胞支持整个HCV生命周期（HepG 2-HFL细胞）。我们发现，与Huh-7和Huh-7.5细胞相比，这些细胞维持HCV感染和传播的能力存在显着差异。此外，当用其他RNA病毒和病毒模拟物攻击时，HepG 2-HFL细胞比Huh-7和Huh-7.5细胞产生更强的抗病毒应答。HCV感染在HepG 2-HFL细胞中引起了强有力的IFN-λ（λ）、ISG和细胞因子应答，但在Huh-7细胞中没有，这表明HepG 2-HFL细胞更忠实地再现了体内对HCV感染的先天免疫应答。利用这种新的模型，我们发现阻断RIG-I样受体通路或IFN-λ信号通路，促进HCV在HepG 2-HFL细胞中的感染和扩散。HepG 2-HFL细胞是研究HCV与先天免疫系统相互作用的一个有前景的新系统，巩固了IFN-λ在肝脏对HCV感染应答中的重要性，并揭示了RIG-I和MDA 5在HCV识别和抑制感染中的非冗余作用。
Hepatitis C virus (HCV) exposure leads to persistent life-long infections characterized by chronic inflammation often developing into cirrhosis and hepatocellular carcinoma. The mechanism by which HCV remains in the liver while inducing an inflammatory and antiviral response remains unclear. While the innate immune response to HCV in patients seem to be quite active, HCV has been shown in cell culture to employ a diverse array of innate immune antagonists, suggesting that current model systems to study interactions between HCV and the innate immune system are not representative of what is happening in vivo. We recently showed that hepatoma-derived HepG2 cells support the entire HCV life cycle if the liver-specific microRNA miR-122 is expressed along with the entry factor CD81 (HepG2-HFL cells). We found that there was a striking difference in these cells’ ability to sustain HCV infection and spread when compared to Huh-7 and Huh-7.5 cells. Additionally, HepG2-HFL cells produced a more robust antiviral response when challenged with other RNA viruses and viral mimetics than Huh-7 and Huh-7.5 cells. HCV infection elicited a potent IFN-λ (lambda), ISG, and cytokine response in HepG2-HFL cells, but not in Huh-7 cells, suggesting that HepG2-HFL cells more faithfully recapitulate the innate immune response to HCV infection in vivo. Using this new model, we found that blocking the RIG-I like receptor pathway or the IFN-λ signaling pathway, promoted HCV infection and spread in HepG2-HFL cells. HepG2-HFL cells represent a promising new system to study the interaction between HCV and the innate immune system, solidifying the importance of IFN-λ in hepatic response to HCV infection and revealing non-redundant roles of RIG-I and MDA5 in HCV recognition and repression of infection.
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影响因子：
5.4
作者：
Errett, John S.;Suthar, Mehul S.;Gale, Michael, Jr.
通讯作者：
Gale, Michael, Jr.
影响因子：
5.4
作者：
Narbus, Christopher M.;Israelow, Benjamin;Evans, Matthew J.
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Evans, Matthew J.
影响因子：
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作者：
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DOI：
10.1073/pnas.220398297
发表时间：
2000-10-24
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
Evans, Matthew J.