How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A.
How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A.
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DOI：
10.1006/viro.2001.0885
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发表时间：
2001-05
期刊：
影响因子：
3.7
通讯作者：
Seng-Lai Tan;M. Katze
中科院分区：
文献类型：
--
作者：
Seng-Lai Tan;M. Katze
干扰素（IFN）通过复杂和间接的机制在细胞中诱导抗病毒状态，其最终直接抑制病毒复制并刺激宿主适应性反应。病毒通常用精心设计的策略来干扰IFN效应分子的诱导以及作用。病毒和IFN成分之间的进化斗争是一个激烈的研究课题，旨在了解病毒的免疫发病机制和IFN信号传导和作用的分子基础。在丙型肝炎病毒（HCV）的情况下，这可能对重组干扰素治疗慢性丙型肝炎的治疗用途有深远的影响。根据丙型肝炎病毒的亚型，目前基于干扰素的治疗方案仅对一小部分慢性丙型肝炎患者有效。因此，HCV研究的圣杯之一是了解病毒可能逃避IFN抗病毒监测并建立持续感染的机制，这最终可能为更好的抗病毒治疗提供新途径。尽管缺乏有效的组织培养系统和合适的HCV感染的动物模型，但基于临床研究和体外实验已经提出了几种机制。这minireview的重点是丙型肝炎病毒NS5A非结构蛋白，这是牵连在发挥作用的HCV耐受干扰素治疗，可能部分通过其抑制细胞干扰素诱导的PKR蛋白激酶的能力。
Interferons (IFNs) induce an antiviral state in the cell through complex and indirect mechanisms, which culminate in a direct inhibition of viral replication and stimulation of the host adaptive responses. Viruses often counteract with elaborate strategies to interfere with the induction as well as action of IFN effector molecules. This evolutionary battle between viruses and IFN components is a subject of intense research aimed at understanding the immunopathogenesis of viruses and the molecular basis of IFN signaling and action. In the case with hepatitis C virus (HCV), this may have profound implications for the therapeutic use of recombinant IFN in treating chronic hepatitis C. Depending on the subtype of HCV, current IFN-based treatment regimens are effective for only a small subset of chronic hepatitis C patients. Thus, one of the Holy Grails in HCV research is to understand the mechanisms by which the virus may evade IFN antiviral surveillance and establish persistent infection, which may eventually provide insights into new avenues for better antiviral therapy. Despite the lack of an efficient tissue culture system and an appropriate animal model for HCV infection, several mechanisms have been proposed based on clinical studies and in vitro experiments. This minireview focuses on the HCV NS5A nonstructural protein, which is implicated in playing a role in HCV tolerance to IFN treatment, possibly in part through its ability to inhibit the cellular IFN-induced PKR protein kinase.