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

作　　者：Jing Zhang Na Wu Na Gao Wenli Yan Ziyang Sheng Dongying Fan Jing An 

机构地区：[1]Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China [2]Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100069, China

出　　处：《Science China(Life Sciences)》2016年第5期487-494,共8页中国科学（生命科学英文版）

基　　金：supported by the National Key Programs on Basic Research of China (2011CB504703);the National Natural Science Foundations of China (81301435, 81471957, 81271839, 81401676);Beijing Natural Science Foundation (7144194)

摘　　要：Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the patho- genesis of severe dengue remains unclear. In this study, we showed that the Racl-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. Racl activities decreased during the early phase and gradually increased by the late phase of infection. Expression of the dominant-negative form of Racl promoted DENV2 entry but inhibited viral as- sembly, maturation and release. Our findings demonstrated that Racl plays an important role in the DENV2 life cycle by reg- ulating actin reorganization in EAhy926 cells. This finding provides further insight into the pathogenesis of severe dengue.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.

关 键 词：dengue virus small Rho GTPase Racl ACTIN vascular endothelial cells 

分 类 号：R373[医药卫生—病原生物学]