title: Newcastle disease virus employs macropinocytosis and Rab5a-dependent intracellular trafficking to infect DF-1 cells.
abstract: Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed. NDV entry into cells triggers Rac1-Pak1 signaling and elicits actin rearrangement and plasma membrane ruffling. Moreover, NDV internalization within macropinosomes and trafficking involve Rab5a-positive vesicles. This is the first report demonstrating that NDV utilizes clathrin-mediated endocytosis and macropinocytosis as alternative endocytic pathways to enter cells. These findings shed new light on the molecular mechanisms underlying NDV entry into cells, and provide potential targets for NDV-mediated therapy in cancer.
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.|Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, P.R. China.
authors.forename: Chan
authors.initials: C
authors.lastname: Ding
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002966:Clathrin / Q000502:physiology; D034281:Dynamins / Q000502:physiology; D004705:Endocytosis; D009522:Newcastle disease virus / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010873:Pinocytosis; D053586:Virus Internalization; D014779:Virus Replication; D020696:rab5 GTP-Binding Proteins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology
chemical_list: D000199:Actins; D002966:Clathrin; D019869:Phosphatidylinositol 3-Kinases; D020696:rab5 GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D034281:Dynamins
keywords: Rab5a; clathrin; endocytosis; macropinocytosis; newcastle disease virus