Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection.
Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection.
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DOI：
10.1371/journal.pone.0089869
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hijikata M
中科院分区：
文献类型：
--
作者：
Tsugawa Y;Kato H;Fujita T;Shimotohno K;Hijikata M
已知几种病毒感染人类肝脏并引起肝炎，但病毒感染肝细胞的干扰素（IFN）反应（对抗病毒感染的第一线防御）尚未明确定义。我们研究了永生化人肝细胞（HuS-E/2细胞）抗RNA病毒感染的先天免疫系统，因为细胞显示出与原代人肝细胞（PHH）相似的早期先天免疫应答。在没有病毒感染的情况下，在PHH和HuS-E/2细胞中观察到IFN-α1基因的低水平组成性表达，而不是IFN-β和IFN-λ，表明IFN-α的特定亚型在人肝细胞中组成性产生。为了研究这种IFN-α在抗病毒应答中的功能作用，在病毒感染前后，研究了细胞中先天免疫相关基因的表达谱，所述细胞具有针对I型IFN受体2（IFNAR 2）或IFN-α本身的中和处理以抑制组成性IFN-α信号传导。作为结果，在未感染的细胞中观察到IFN诱导基因的基础水平表达的明显降低。当检测对感染丙型肝炎病毒（HCV）的细胞的抑制作用时，观察到IFN刺激的基因表达的显著降低和HCV初始复制的增强，表明IFN-α的稳态产生在放大抗病毒应答以控制RNA病毒感染在人肝细胞中的传播中起作用。
Several viruses are known to infect human liver and cause the hepatitis, but the interferon (IFN) response, a first-line defense against viral infection, of virus-infected hepatocytes is not clearly defined yet. We investigated innate immune system against RNA viral infection in immortalized human hepatocytes (HuS-E/2 cells), as the cells showed similar early innate immune responses to primary human hepatocytes (PHH). The low-level constitutive expression of IFN-α1 gene, but not IFN-β and IFN-λ, was observed in both PHH and HuS-E/2 cells in the absence of viral infection, suggesting a particular subtype(s) of IFN-α is constitutively produced in human hepatocytes. To examine the functional role of such IFN-α in the antiviral response, the expression profiles of innate immune-related genes were studied in the cells with the treatment of neutralization against type I IFN receptor 2 (IFNAR2) or IFN-α itself to inhibit the constitutive IFN-α signaling before and after virus infection. As the results, a clear reduction of basal level expression of IFN-inducible genes was observed in uninfected cells. When the effect of the inhibition on the cells infected with hepatitis C virus (HCV) was examined, the significant decrease of IFN stimulated gene expression and the enhancement of initial HCV replication were observed, suggesting that the steady-state production of IFN-α plays a role in amplification of antiviral responses to control the spread of RNA viral infection in human hepatocytes.
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DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
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DOI：
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发表时间：
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期刊：
The Journal of experimental medicine
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影响因子：
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