title: Caveolin-1-mediated Japanese encephalitis virus entry requires a two-step regulation of actin reorganization.
abstract: To investigate the detailed mechanism of Japanese encephalitis virus (JEV) cell entry.
  
  
  
  Utilize a siRNA library targeting cellular membrane trafficking genes to identify key molecules that mediate JEV entry into human neuronal cells.
  
  
  
  JEV enters human neuronal cells by caveolin-1-mediated endocytosis, which depends on a two-step regulation of actin cytoskeleton remodeling triggered by RhoA and Rac1: RhoA activation promoted the phosphorylation of caveolin-1, and then Rac1 activation facilitated caveolin-associated viral internalization. Specifically, virus attachment activates the EGFR-PI3K signaling pathway, thereby leading to RhoA activation.
  
  
  
  This work provides a detailed picture of the entry route and intricate cellular events following the entry of JEV into human neuronal cells, and promotes a better understanding of JEV entry.
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Qingqiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Medical Microbiology & Parasitology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Mingmei
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Shenglin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Xijing
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China.
authors.forename: Youheng
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China.
authors.forename: Zhongtian
authors.initials: Z
authors.lastname: Qi
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D051339:Actin Depolymerizing Factors / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D051242:Caveolin 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity / Q000502:physiology*; D004672:Encephalitis, Japanese / Q000821:virology; D004705:Endocytosis / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D008018:Life Cycle Stages / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000821:virology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D053585:Virus Attachment; D053586:Virus Internalization / Q000187:drug effects*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism / Q000494:pharmacology
chemical_list: D051339:Actin Depolymerizing Factors; C495540:CAV1 protein, human; D051242:Caveolin 1; D026901:Membrane Transport Proteins; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; C066737:RHOA protein, human; D002784:Cholesterol; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D034285:Dynamin II
keywords: Caveolin-1; EGFR; Japanese encephalitis virus; actin regulation; endocytosis; neuronal cells