The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1.
The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1.
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单纯疱疹病毒 2 的 Us2 基因产物通过靶向 TAK1 来调节 NF-kappaB 激活。
DOI：
10.1038/s41598-017-08856-4
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发表时间：
2017-08-21
影响因子：
4.6
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Lu X;Huang C;Zhang Y;Lin Y;Wang X;Li Q;Liu S;Tang J;Zhou L
2型单纯疱疹病毒是世界上最常见的性传播病原体之一，2型单纯疱疹病毒感染会引发细胞因子和趋化因子的产生。然而，对于哪些HSV-2基因参与NF-κB信号的调控以及涉及的机制知之甚少。在HSV-2独特的短（Us）区域的筛选中，我们观察到HSV-2 Us2激活NF-κB信号。我们还发现，Us2缺乏会降低HSV-2 WT介导的NF-κB活化和细胞因子和趋化因子的产生，而Us2过表达则会产生相反的作用。共免疫沉淀表明Us2与TGF-β活化激酶1 （TAK1）相互作用，TAK1是NF-κB活化所必需的丝氨酸/苏氨酸激酶，并且Us2具有调节TAK1介导的途径并诱导TAK1下游信号通路的能力。进一步的研究证实，Us2诱导TAK1磷酸化，从而激活TAK1介导的下游信号通路。Us2在Us2缺陷突变体和HSV-2 WT感染小鼠中也证实了Us2在HSV-2诱导的NF-κB通路中的作用。我们的研究结果表明，HSV-2 Us2基因产物与TAK1结合，积极调节NF-κB信号，并首次提供了分子机制的见解。
HSV-2 is one of the most common sexually transmitted pathogens worldwide and HSV-2 infection triggers cytokine and chemokine production. However, little is known about which HSV-2 genes engage in the regulation of NF-κB signaling and what mechanisms are involved. In a screen of the unique short (Us) regions of HSV-2, we observed that HSV-2 Us2 activates NF-κB signaling. We additionally indicated that deficiencies of Us2 decrease HSV-2 WT mediated NF-κB activation and cytokine and chemokine production, and overexpression of Us2 showed opposite effects. Co-immunoprecipitations indicated that Us2 interacted with TGF-β activated kinase 1 (TAK1), a serine/threonine kinase essential for NF-κB activation, and Us2 has the ability to regulate the TAK1-mediated pathway and induces TAK1 downstream signaling. Further studies verified that Us2 induced the phosphorylation of TAK1, resulting in the activation of TAK1 mediated downstream signaling. The role of Us2 in HSV-2 induced NF-κB pathways was also confirmed in the Us2-deficient mutant and HSV-2 WT infected mice. Our results indicate that HSV-2 Us2 gene product binds to TAK1 to positively regulate NF-κB signaling and, for the first time, provide insights into the molecular mechanism.
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影响因子：
6.7
作者：
Martinelli E;Tharinger H;Frank I;Arthos J;Piatak M Jr;Lifson JD;Blanchard J;Gettie A;Robbiani M
通讯作者：
Robbiani M
影响因子：
5.4
作者：
Hargett, Danna;Rice, Stephen;Bachenheimer, Steven L.
通讯作者：
Bachenheimer, Steven L.
DOI：
10.1073/pnas.1110946108
发表时间：
2011-11-29
影响因子：
11.1
作者：
Li, Qi;Yan, Jie;Wang, Yan-Yi
通讯作者：
Wang, Yan-Yi
影响因子：
25.7
作者：
Liu, Shi;Peng, Nanfang;Zhu, Ying
通讯作者：
Zhu, Ying
DOI：
10.1073/pnas.0801617105
发表时间：
2008-08-12
影响因子：
11.1
作者：
Liu, XueQiao;Fitzgerald, Katherine;Knipe, David M.
通讯作者：
Knipe, David M.