STAU1 binds to IBDV genomic double-stranded RNA and promotes viral replication via attenuation of MDA5-dependent β interferon induction
STAU1 binds to IBDV genomic double-stranded RNA and promotes viral replication via attenuation of MDA5-dependent β interferon induction
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STAU1 与 IBDV 基因组双链 RNA 结合，并通过减弱 MDA5 依赖性 β 干扰素诱导来促进病毒复制
DOI：
10.1096/fj.201800062rr
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Hebin Liu
中科院分区：
文献类型：
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作者：
Chengjin Ye;Zhaoli Yu;Yiwei Xiong;Yu Wang;Yina Ruan;Yueping Guo;Mianmian Chen;Shilu Luan;Enli Zhang;Hebin Liu
传染性法氏囊病病毒（IBDV）感染触发IIFN型的诱导，其由黑色素瘤分化相关蛋白5识别病毒基因组双链RNA（dsRNA）介导。然而，IBDV克服I型IFN抗病毒应答的机制仍然缺乏表征。在此，我们证明了IBDV基因组dsRNA在体外和体内选择性地与宿主细胞RNA结合蛋白Staufen 1（STAU 1）结合。将病毒dsRNA结合区定位于STAU 1的N末端部分（残基1-468）。STAU 1的下调损害了IBDV复制并增强了响应IBDV感染的IFN-β转录，而对病毒附着于宿主细胞和细胞进入几乎没有影响。相反，STAU 1的过表达而不是IBDV dsRNA结合缺陷型STAU 1突变体（469-702）导致IBDV dsRNA诱导的IFN-β启动子活性的抑制。此外，我们发现STAU 1与IBDV dsRNA的结合降低了体外黑素瘤分化相关蛋白5而不是VP 3与IBDV dsRNA的结合。最后，我们发现STAU 1和VP 3以相加的方式抑制响应IBDV感染的IFN-β基因转录。总的来说，这些发现为IBDV逃避宿主IFN抗病毒反应所使用的逃避策略提供了新的见解。叶，C.，于志，熊，Y.，王玉，Ruan，Y.，Guo，Y.，中国科学院，陈美，Luan，S.，Zhang，E.，Liu，H. STAU 1与IBDV基因组双链RNA结合，并通过减弱MDA 5依赖性β干扰素诱导来促进病毒复制。FASEB J. 33，286-300（2019）。www.fasebj.org
Infectious bursal disease virus (IBDV) infection triggers the induction of type IIFN, which is mediated by melanoma differentiation‐associated protein 5 recognition of the viral genomic double‐stranded RNA (dsRNA). However, the mechanism of IBDV overcoming the type I IFN antiviral response remains poorly characterized. Here, we show that IBDV genomic dsRNA selectively binds to the host cellular RNA binding protein Staufen1 (STAU1)in vitroandin vivo. The viral dsRNA binding region was mapped to the N‐terminal moiety of STAU1 (residues 1–468). Down‐regulation of STAU1 impaired IBDV replication and enhanced IFN‐β transcription in response to IBDV infection, while having little effect on the viral attachment to the host cells and cellular entry. Conversely, over‐expression of STAU1 but not the IBDV dsRNA–binding deficient STAU1 mutant (469–702) led to a suppression of IBDV dsRNA–induced IFN‐β promoter activity. Moreover, we found that the binding of STAU1 to IBDV dsRNA decreased the association of melanoma differentiation‐associated protein 5 but not VP3 with the IBDV dsRNAin vitro. Finally, we showed that STAU1 and VP3 suppressed IFN‐β gene transcription in response to IBDV infection in an additive manner. Collectively, these findings provide a novel insight into the evasive strategies used by IBDV to escape the host IFN antiviral response.—Ye, C., Yu, Z., Xiong, Y., Wang, Y., Ruan, Y., Guo, Y., Chen, M., Luan, S., Zhang, E., Liu, H. STAU1 binds to IBDV genomic double‐stranded RNA and promotes viral replication via attenuation of MDA5‐dependent β interferon induction. FASEB J. 33, 286–300 (2019). www.fasebj.org