Antiviral activity of human OASL protein is mediated by enhancing signaling of the RIG-I RNA sensor.

Antiviral activity of human OASL protein is mediated by enhancing signaling of the RIG-I RNA sensor.
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DOI:
10.1016/j.immuni.2014.05.007
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发表时间:
2014-06-19
期刊:
影响因子:
32.4
通讯作者:
Sarkar, Saumendra N.
Sarkar, Saumendra N.
中科院分区:
医学1区
文献类型:
--
作者:
Zhu, Jianzhong;Zhang, Yugen;Ghosh, Arundhati;Cuevas, Rolando A.;Forero, Adriana;Dhar, Jayeeta;Ibsen, Mikkel Soes;Schmid-Burgk, Jonathan Leo;Schmidt, Tobias;Ganapathiraju, Madhavi K.;Fujita, Takashi;Hartmann, Rune;Barik, Sailen;Hornung, Veit;Coyne, Carolyn B.;Sarkar, Saumendra N.

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病毒感染是通过维甲酸诱导基因I(RIG-I,也称为DDX58)在细胞质中感应的,它需要RNA和多聚泛素结合来诱导I型干扰素(IFN),并激活细胞天然免疫。我们发现,人干扰素诱导的寡腺苷合成酶样蛋白(OASL)具有抗病毒活性,并通过模拟多聚泛素介导RIG-I的激活。OASL表达的缺失降低了RIG-I信号转导,增强了病毒在人类细胞中的复制。相反,OASL的表达以rig-I依赖的方式抑制了一些病毒的复制,并增强了rig-I介导的干扰素的诱导。OASL与RIG-I相互作用和共定位,并通过其C端泛素样结构域特异性增强RIG-I信号。来自Oasl2基因缺陷小鼠的骨髓来源的巨噬细胞表明,在两个人OASL的小鼠同源基因中,Oasl2在功能上与人OASL相似。我们的发现表明,人类OASL通过增强RIG-I激活来促进宿主抗病毒反应的机制。
Virus infection is sensed in the cytoplasm by retinoic acid-inducible gene I (RIG-I, also known as DDX58), which requires RNA and polyubiquitin binding to induce type I interferon (IFN), and activate cellular innate immunity. We show that the human IFN-inducible oligoadenylate synthetases-like (OASL) protein had antiviral activity and mediated RIG-I activation by mimicking polyubiquitin. Loss of OASL expression reduced RIG-I signaling and enhanced virus replication in human cells. Conversely, OASL expression suppressed replication of a number of viruses in a RIG-I-dependent manner and enhanced RIG-I-mediated IFN induction. OASL interacted and colocalized with RIG-I, and through its C-terminal ubiquitin-like domain specifically enhanced RIG-I signaling. Bone marrow derived macrophages from mice deficient for Oasl2 showed that among the two mouse orthologs of human OASL; Oasl2 is functionally similar to human OASL. Our findings show a mechanism by which human OASL contributes to host antiviral responses by enhancing RIG-I activation.
RIG-I 样受体的免疫信号传导。
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