title: Susceptibility of human embryonic stem cell-derived neural cells to Japanese encephalitis virus infection.
abstract: Pluripotent human embryonic stem cells (hESCs) can be efficiently directed to become immature neuroepithelial precursor cells (NPCs) and functional mature neural cells, including neurotransmitter-secreting neurons and glial cells. Investigating the susceptibility of these hESCs-derived neural cells to neurotrophic viruses, such as Japanese encephalitis virus (JEV), provides insight into the viral cell tropism in the infected human brain. We demonstrate that hESC-derived NPCs are highly vulnerable to JEV infection at a low multiplicity of infection (MOI). In addition, glial fibrillary acid protein (GFAP)-expressing glial cells are also susceptible to JEV infection. In contrast, only a few mature neurons were infected at MOI 10 or higher on the third day post-infection. In addition, functional neurotransmitter-secreting neurons are also resistant to JEV infection at high MOI. Moreover, we discover that vimentin intermediate filament, reported as a putative neurovirulent JEV receptor, is highly expressed in NPCs and glial cells, but not mature neurons. These results indicate that the expression of vimentin in neural cells correlates to the cell tropism of JEV. Finally, we further demonstrate that membranous vimentin is necessary for the susceptibility of hESC-derived NPCs to JEV infection.
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shih-Cheng
authors.initials: SC
authors.lastname: Shen
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ching-I
authors.initials: CI
authors.lastname: Shen
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ho
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan; Center for General Education, Tunghai University, Taichung, Taiwan; Graduate School of Nursing, Hung-Kuang University, Taichung, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Sheng-Mei
authors.initials: SM
authors.lastname: Chen
authors.affiliation: Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Hsiu-Chin
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ping-Shan
authors.initials: PS
authors.lastname: Lai
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Su
mesh_terms: D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D004664:Encephalitis Virus, Japanese / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D046569:Neuroepithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000821:virology; D014746:Vimentin / Q000378:metabolism; D056189:Viral Tropism
chemical_list: D014746:Vimentin