LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection

LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection
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DOI:
10.1073/pnas.1203405109
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发表时间:
2012-07-17
影响因子:
11.1
通讯作者:
Shu, Hong-Bing
Shu, Hong-Bing
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li, Ying;Chen, Rui;Shu, Hong-Bing

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模式识别受体对病毒核酸的识别启动I型IFN诱导和先天抗病毒免疫反应。本研究表明,LSm14A是参与加工体RNA加工的LSm家族成员,可与合成或病毒RNA和DNA结合,介导IRF3激活和ifn - β诱导。LSm14A的敲低抑制胞质RNA和dna触发I型IFN的产生和细胞抗病毒反应。此外,LSm14A对于RNA或DNA病毒感染后早期诱导ifn - β至关重要。我们进一步发现,LSm14A介导的ifn - β诱导在RNA或DNA病毒感染后分别需要RIG-I-VISA或MITA,病毒感染导致LSm14A易位到RIG-I、VISA和MITA所在的过氧化物酶体上。这些发现表明LSm14A是病毒RNA和DNA的传感器,在病毒感染早期启动ifn - β诱导中起重要作用。
Recognition of viral nucleic acids by pattern recognition receptors initiates type I IFN induction and innate antiviral immune response. Here we show that LSm14A, a member of the LSm family involved in RNA processing in the processing bodies, binds to synthetic or viral RNA and DNA and mediates IRF3 activation and IFN-beta induction. Knockdown of LSm14A inhibits cytosolic RNA- and DNA-trigger type I IFN production and cellular antiviral response. Moreover, LSm14A is essential for early-phase induction of IFN-beta after either RNA or DNA virus infection. We further found that LSm14A-mediated IFN-beta induction requires RIG-I-VISA or MITA after RNA or DNA virus infection, respectively, and viral infection causes translocation of LSm14A to peroxisomes, where RIG-I, VISA, and MITA are located. These findings suggest that LSm14A is a sensor for both viral RNA and DNA and plays an important role in initiating IFN-beta induction in the early phase of viral infection.