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-microfilam...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.展开更多
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)
文摘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.
