title: Small G Rac1 is involved in replication cycle of dengue serotype 2 virus in EAhy926 cells via the regulation of actin cytoskeleton.
abstract: 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.
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China. anjing@ccmu.edu.cn.|Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, 100069, China. anjing@ccmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: An
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000330:Aedes; D000818:Animals; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D003716:Dengue Virus / Q000502:physiology*; D047630:Depsipeptides / Q000494:pharmacology; D008561:Membrane Fusion / Q000187:drug effects; D014779:Virus Replication / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
chemical_list: D047630:Depsipeptides; C057531:jasplakinolide; D015638:Cytochalasin D; D020830:rac1 GTP-Binding Protein
keywords: actin; dengue virus; small Rho GTPase Rac1; vascular endothelial cells