The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.
The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.
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DOI：
10.1371/journal.pone.0016870
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发表时间：
2011-02-09
期刊：
影响因子：
3.7
通讯作者：
Sadzot-Delvaux C
中科院分区：
文献类型：
--
作者：
Vandevenne P;Lebrun M;El Mjiyad N;Ote I;Di Valentin E;Habraken Y;Dortu E;Piette J;Sadzot-Delvaux C
先天免疫反应构成宿主防御的第一道防线，限制病毒传播，并在适应性免疫反应的激活中起重要作用。病毒组分被特异性宿主病原体识别受体识别，触发IRF 3的激活。IRF 3沿着NF-κB，是IFN-β表达的关键调节因子。到目前为止，IRF 3在水痘-带状疱疹病毒（VZV）感染期间激活先天免疫应答中的作用研究很少。在这项工作中，我们首次证明了VZV快速诱导IRF 3的非典型磷酸化，这是抑制性的，因为它阻止了随后的IRF 3同源二聚化和靶基因的诱导。使用不能表达病毒激酶ORF 47 p的突变病毒，我们证明了（i）IRF 3缓慢迁移形式消失;（ii）IRF 3在丝氨酸396上再次磷酸化并恢复形成同源二聚体的能力;（iii）IRF 3靶基因如IFN-β和ISG 15 mRNA的量大于用野生型病毒感染的细胞;和（iv）IRF 3与ORF 47 p物理相互作用。这些数据使我们假设病毒激酶ORF 47 p参与VZV感染期间IRF 3的非典型磷酸化，这阻止了其同源二聚化和随后对靶基因如IFN-β和ISG 15的诱导。
The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-κB, is a key regulator of IFN-β expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-β and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-β and ISG15.
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影响因子：
5.4
作者：
El Mjiyad, Nadia;Bontems, Sebastien;Sadzot-Delvaux, Catherine
通讯作者：
Sadzot-Delvaux, Catherine
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
影响因子：
5.4
作者：
Jones, Jeremy O.;Arvin, Ann M.
通讯作者：
Arvin, Ann M.
影响因子：
5.4
作者：
Abendroth, A;Lin, I;Arvin, AM
通讯作者：
Arvin, AM
影响因子：
5.3
作者：
Lin, RT;Heylbroeck, C;Hiscott, J
通讯作者：
Hiscott, J