title: Dengue virus infection increases microglial cell migration.
abstract: Activated microglial cells are present in dengue virus (DENV)-infected brains; however, the possible effects of DENV on microglia remain unclear. Here, we demonstrated DENV caused infection, including viral entry, RNA replication, viral protein expression, and virus release, in the murine microglial cell line BV2. DENV infection caused an increase in the formation of the multipolar phenotype in vitro and in vivo without affecting cell growth and cytotoxicity. DENV infection considerably increased cell motility and disrupting either actin filaments or clathrin retarded such effect. Increase in cell migration was only occurred by DENV infection following a clathrin-regulated endocytosis of DENV entry. Ultraviolet-inactivated DENV did not affect cell migration, and pharmacologically blocking toll-like receptor (TLR) 3 and TLR3-related signaling pathways reduced the DENV-induced increase in cell migration. These results demonstrate an advanced effect of DENV infection on microglial migration via a mechanism involving viral entry, RNA release, and TLR3 signal activation.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.|Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Jhan
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Tsung-Ting
authors.initials: TT
authors.lastname: Tsai
authors.affiliation: Translational Research Center, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Nursing, Chung Hwa University of Medical Technology, Tainan, 717, Taiwan.
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Cheng
authors.affiliation: The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Yi-Chao
authors.identifier: 0000-0003-3451-183X
authors.initials: YC
authors.lastname: Lee
authors.affiliation: The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Chiung-Yuan
authors.initials: CY
authors.lastname: Ko
authors.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.|Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.|Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan, 701, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.|Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.|Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan, 701, Taiwan.
authors.forename: Chih-Peng
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.|Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Liang-Tzung
authors.initials: LT
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. cflin2014@tmu.edu.tw.|Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. cflin2014@tmu.edu.tw.|Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan, 701, Taiwan. cflin2014@tmu.edu.tw.
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002966:Clathrin / Q000378:metabolism; D003715:Dengue / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D004705:Endocytosis; D006801:Humans; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D008954:Models, Biological; D012367:RNA, Viral / Q000235:genetics*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D002966:Clathrin; D012367:RNA, Viral; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3