roles of small gtpase rac1 in the regulation of actin cytoskeleton during dengue virus infection角色的小gtpase rac1调节肌动蛋白细胞骨架的登革病毒感染.pdfVIP

Roles of Small GTPase Rac1 in the Regulation of Actin Cytoskeleton during Dengue Virus Infection 1 1 1 2 3 3 3 Jia-Li Wang , Jun-Lei Zhang , Wei Chen , Xiao-Feng Xu , Na Gao , Dong-Ying Fan , Jing An * 1 Department of Microbiology, Third Military Medical University, Chongqing, People’s Republic of China, 2 Department of Genetics, Third Military Medical University, Chongqing, People’s Republic of China, 3 Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China Abstract Background: Increased vascular permeability is a hallmark feature in severe dengue virus (DV) infection, and dysfunction of endothelial cells has been speculated to contribute in the pathogenesis of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Rho-family GTPase Rac1 is a significant element of endothelial barrier function regulation and has been implicated in the regulation of actin remodeling and intercellular junction formation. Yet there is little evidence linking Rac1 GTPase to alteration in endothelial cell function induced by DV infection. Methods and Findings: Here, we showed that actin is essential for DV serotype 2 (DV2) entry into and release from ECV304 cells, and Rac1 signaling is involved these processes. At early infection, actin cytoskeleton rearranged significantly during 1 hour post infection, and disrupting actin filament dynamics with jasplakinolide or cytochalasin D reduced DV2 entry. DV2 entry induced reduction of Rac1 activity within 1 hour post infection. The expression of dominant-negative forms of Rac1 established that DV2 entry is n