title: Heat shock cognate protein 70 isoform D is required for clathrin-dependent endocytosis of Japanese encephalitis virus in C6/36 cells.
abstract: Japanese encephalitis virus (JEV), one of encephalitic flaviviruses, is naturally transmitted by mosquitoes. During infection, JEV generally enters host cells via receptor-mediated clathrin-dependent endocytosis that requires the 70 kDa heat-shock protein (Hsp70). Heat-shock cognate protein 70 (Hsc70) is one member of the Hsp70 family and is constitutively expressed; thus, it may be expressed under physiological conditions. In C6/36 cells, Hsc70 is upregulated in response to JEV infection. Since Hsc70 shows no relationship with viruses attaching to the cell surface, it probably does not serve as the receptor according to our results in the present study. In contrast, Hsc70 is evidently associated with virus penetration into the cell and resultant acidification of intracellular vesicles. It suggests that Hsc70 is highly involved in clathrin-mediated endocytosis, particularly at the late stage of viral entry into host cells. Furthermore, we found that Hsc70 is composed of at least three isoforms, including B, C and D; of these, isoform D helps JEV to penetrate C6/36 cells via clathrin-mediated endocytosis. This study provides relevant evidence that sheds light on the regulatory mechanisms of JEV infection in host cells, especially on the process of clathrin-mediated endocytosis.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan.
authors.forename: Ching-Kai
authors.initials: CK
authors.lastname: Chuang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan.
authors.forename: Tsong-Han
authors.initials: TH
authors.lastname: Yang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan.
authors.forename: Tien-Huang
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan.
authors.forename: Chao-Fu
authors.initials: CF
authors.lastname: Yang
authors.affiliation: Department of Public Health and Parasitology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan.|Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan.
authors.forename: Wei-June
authors.initials: WJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D006224:Cricetinae; D009033:Culicidae / Q000821:virology; D004664:Encephalitis Virus, Japanese / Q000378:metabolism*; D004672:Encephalitis, Japanese / Q000378:metabolism* / Q000821:virology; D004705:Endocytosis / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D053586:Virus Internalization
chemical_list: D002966:Clathrin; D018840:HSP70 Heat-Shock Proteins; D020033:Protein Isoforms