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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.
AuthorsShih-Cheng Shen, Ching-I Shen, Ho Lin, Chun-Jung Chen, Chia-Yu Chang, Sheng-Mei Chen, Hsiu-Chin Lee, Ping-Shan Lai, Hong-Lin Su
JournalPloS one (PLoS One) Vol. 9 Issue 12 Pg. e114990 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID25517725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Vimentin
Topics
  • Cell Line
  • Embryonic Stem Cells (cytology)
  • Encephalitis Virus, Japanese (physiology)
  • Gene Expression Regulation
  • Humans
  • Neuroepithelial Cells (cytology, metabolism, virology)
  • Neuroglia (cytology, metabolism, virology)
  • Vimentin (metabolism)
  • Viral Tropism

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