Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I
Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I
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DOI：
10.1128/jvi.79.5.2689-2699.2005
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Gale, M
中科院分区：
文献类型：
--
作者：
Stumper, R;Loo, YM;Gale, M
诱导α/β干扰素产生并参与细胞内免疫防御的病毒应答信号通路影响许多病毒感染的结果。触发这些防御的过程以及它们对宿主对特定病毒病原体的容许性的影响还不清楚。我们表明，结构化的丙型肝炎病毒（HCV）基因组RNA激活干扰素调节因子3（IRF 3），从而诱导干扰素在培养细胞。这种反应在选择允许HCV RNA复制的细胞中不存在。包括遗传互补的研究表明，宽容是由于RIG-I，干扰素诱导的细胞DExD/H盒RNA解旋酶的突变失活。其解旋酶结构域结合HCV RNA并通过其半胱天冬酶募集结构域同源物转导IRF 3的活化信号。因此，RIG-I是一种病原体受体，其调节细胞对HCV复制的容许性，并且作为干扰素应答基因，可能在用于治疗HCV感染的基于干扰素的疗法中发挥关键作用。
Virus-responsive signaling pathways that induce alpha/beta interferon production and engage intracellular immune defenses influence the outcome of many viral infections. The processes that trigger these defenses and their effect upon host permissiveness for specific viral pathogens are not well understood. We show that structured hepatitis C virus (HCV) genomic RNA activates interferon regulatory factor 3 (IRF3), thereby inducing interferon in cultured cells. This response is absent in cells selected for permissiveness for HCV RNA replication. Studies including genetic complementation revealed that permissiveness is due to mutational inactivation of RIG-I, an interferon-inducible cellular DExD/H box RNA helicase. Its helicase domain binds HCV RNA and transduces the activation signal for IRF3 by its caspase recruiting domain homolog. RIG-I is thus a pathogen receptor that regulates cellular permissiveness to HCV replication and, as an interferon-responsive gene, may play a key role in interferon-based therapies for the treatment of HCV infection.