Small G Rac1 is involved in replication cycle of dengue serotype 2 virus in EAhy926 cells via the regulation of actin cytoskeleton.

Small G Rac1 is involved in replication cycle of dengue serotype 2 virus in EAhy926 cells via the regulation of actin cytoskeleton.
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Small G Rac1通过调节肌动蛋白细胞骨架参与EAhy926细胞中登革热血清型2病毒的复制周期

DOI:
10.1007/s11427-016-5042-5
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发表时间:
2016-05
期刊:
Science China. Life sciences
影响因子:
--
通讯作者:
An J
An J
中科院分区:
其他
文献类型:
--
作者:
Zhang J;Wu N;Gao N;Yan W;Sheng Z;Fan D;An J

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出血是严重登革热的临床特征,可能是由于血管通透性增加。然而,严重登革热的发病机制仍不清楚。在本研究中,我们发现Rac 1-微丝信号通路参与了DENV血清型2(DENV 2)感染EAhy 926细胞的过程。DENV 2感染诱导肌动蛋白组织的动态变化,并且用细胞松弛素D或Jasplakinase处理破坏微丝动力学,减少DENV 2进入,并抑制DENV 2组装和成熟。Rac 1活性在感染早期下降,后期逐渐上升。Rac 1的显性阴性形式的表达促进了DENV 2的进入,但抑制了病毒的组装、成熟和释放。我们的研究结果表明,Rac 1通过调节EAhy 926细胞中的肌动蛋白重组在DENV 2生命周期中起着重要作用。这一发现为严重登革热的发病机制提供了进一步的见解。
Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the pathogenesis of severe dengue remains unclear. In this study, we showed that the Rac1-microfilament signal pathway was involved in the process of DENV serotype 2 (DENV2) infection in EAhy926 cells. DENV2 infection induced dynamic changes in actin organization, and treatment with Cytochalasin D or Jasplakinolide disrupted microfilament dynamics, reduced DENV2 entry, and inhibited DENV2 assembly and maturation. Rac1 activities decreased during the early phase and gradually increased by the late phase of infection. Expression of the dominant-negative form of Rac1 promoted DENV2 entry but inhibited viral assembly, maturation and release. Our findings demonstrated that Rac1 plays an important role in the DENV2 life cycle by regulating actin reorganization in EAhy926 cells. This finding provides further insight into the pathogenesis of severe dengue.
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