DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection.
DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection.
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DOI：
10.1038/s41598-017-17689-0
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发表时间：
2017-12-12
影响因子：
4.6
通讯作者：
Grandvaux N
中科院分区：
文献类型：
--
作者：
Robitaille AC;Caron E;Zucchini N;Mukawera E;Adam D;Mariani MK;Gélinas A;Fortin A;Brochiero E;Grandvaux N
宿主的抗病毒反应涉及干扰素和促炎细胞因子的诱导，但也涉及细胞死亡途径的激活，包括细胞凋亡，以限制病毒复制和传播。这种宿主防御受到严格调节，以消除感染，同时限制与病毒发病机制相关的组织损伤。翻译后修饰，最显著的是磷酸化，是抗病毒防御的关键调节剂，这意味着蛋白磷酸酶的重要作用。在这里，我们研究了双特异性磷酸酶1（DUSP 1）在宿主防御人类呼吸道合胞病毒（RSV）（一种肺炎病毒科的致病性病毒）和仙台病毒（SeV）（一种正在开发作为抗RSV疫苗载体的模型病毒）中的作用。我们发现DUSP 1在被蛋白酶体降解之前被上调。DUSP 1不抑制抗病毒反应，但负调节病毒诱导的JNK/p38 MAPK磷酸化。与JNK相互作用蛋白1支架蛋白的相互作用阻止了DUSP 1对JNK的去磷酸化，这可能解释了AP-1活化和下游细胞因子产生受到保护而不受DUSP 1抑制。重要的是，DUSP 1促进SeV诱导的细胞凋亡并抑制RSV感染细胞的细胞迁移。总的来说，我们的数据揭示了DUSP 1在RSV和SeV感染期间调节组织损伤和修复的先前未被认识的选择性作用。
The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveils a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.
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影响因子：
4.4
作者：
Fink, Karin;Duval, Annick;Grandvaux, Nathalie
通讯作者：
Grandvaux, Nathalie
灭活仙台病毒诱导激素抗性人前列腺癌PC3细胞凋亡
影响因子：
3.5
作者：
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影响因子：
15.3
作者：
Arbour, Nathalie;Naniche, Denise;Homann, Dirk;Davis, Roger J;Flavell, Richard A;Oldstone, Michael B A
通讯作者：
Oldstone, Michael B A
影响因子：
2.7
作者：
Afonso CL;Amarasinghe GK;Bányai K;Bào Y;Basler CF;Bavari S;Bejerman N;Blasdell KR;Briand FX;Briese T;Bukreyev A;Calisher CH;Chandran K;Chéng J;Clawson AN;Collins PL;Dietzgen RG;Dolnik O;Domier LL;Dürrwald R;Dye JM;Easton AJ;Ebihara H;Farkas SL;Freitas-Astúa J;Formenty P;Fouchier RA;Fù Y;Ghedin E;Goodin MM;Hewson R;Horie M;Hyndman TH;Jiāng D;Kitajima EW;Kobinger GP;Kondo H;Kurath G;Lamb RA;Lenardon S;Leroy EM;Li CX;Lin XD;Liú L;Longdon B;Marton S;Maisner A;Mühlberger E;Netesov SV;Nowotny N;Patterson JL;Payne SL;Paweska JT;Randall RE;Rima BK;Rota P;Rubbenstroth D;Schwemmle M;Shi M;Smither SJ;Stenglein MD;Stone DM;Takada A;Terregino C;Tesh RB;Tian JH;Tomonaga K;Tordo N;Towner JS;Vasilakis N;Verbeek M;Volchkov VE;Wahl-Jensen V;Walsh JA;Walker PJ;Wang D;Wang LF;Wetzel T;Whitfield AE;Xiè JT;Yuen KY;Zhang YZ;Kuhn JH
通讯作者：
Kuhn JH
影响因子：
4.8
作者：
Di, Anke;Kawamura, Takeshi;Malik, Asrar B.
通讯作者：
Malik, Asrar B.