Glycosylation of classical swine fever virus Erns is essential for binding double-stranded RNA and preventing interferon-beta induction

Glycosylation of classical swine fever virus Erns is essential for binding double-stranded RNA and preventing interferon-beta induction
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DOI:
10.1016/j.virusres.2009.09.011
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发表时间:
2009-12-01
期刊:
影响因子:
5
通讯作者:
Pan, Zishu
Pan, Zishu
中科院分区:
医学3区
文献类型:
--
作者:
Luo, Xuelian;Pan, Ruangang;Pan, Zishu

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宿主细胞感知病毒复制过程中产生的双链 RNA (dsRNA),并启动 I 型干扰素 (IFN-α/β) 产生,从而导致随后的抗病毒反应。许多病毒,包括猪瘟病毒 (CSFV),已经开发出对抗 IFN-α/β 反应的策略。在本研究中,我们探讨了 CSFV E-rns 糖蛋白在抑制 dsRNA [poly(IC)] 诱导的 IFN-β 产生中的作用。我们的结果表明,CSFV E-rns 可以与外源 dsRNA 结合并抑制 dsRNA 诱导的 IFN-β 产生,但无法抑制 TRIF 触发的 IFN-β 产生。我们的数据表明,IFN-β 诱导的抑制发生在 TLR3 信号通路的起始步骤。我们还表明,E-rns 的去糖基化使其无法与 dsRNA 结合,因此无法抑制 dsRNA 诱导的 IFN-β 产生。综上所述,这些结果表明 CSFV E-rns 的 N-聚糖对于 E-rns 阻断 IFN-β 诱导至关重要。 (C) 2009 Elsevier B.V. 保留所有权利。
Host cells sense double-stranded RNA (dsRNA) produced during viral replication and initiate type I interferon (IFN-alpha/beta) production, leading to subsequent antiviral responses. Many viruses, including classical swine fever virus (CSFV), have developed strategies for counteracting the IFN-alpha/beta response. In this study, we explored the role of the CSFV E-rns glycoprotein in the inhibition of IFN-beta production induced by dsRNA [poly(IC)]. Our results demonstrated that CSFV E-rns could bind to exogenous dsRNA and inhibit dsRNA-induced IFN-beta production but failed to inhibit TRIF-triggered IFN-beta production. Our data suggest that the inhibition of IFN-beta induction occurred at the initial step of the TLR3 signaling pathway. We also showed that deglycosylation of E-rns rendered it unable to bind to dsRNA, and thus unable to inhibit dsRNA-induced IFN-beta production. Taken together, these results indicated that N-glycan of CSFV E-rns is essential for E-rns blocking of IFN-beta induction. (C) 2009 Elsevier B.V. All rights reserved.