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Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress
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Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress
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Journal Article
Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress
2017
Overview
Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem/progenitor cells. It is a well-known fact that JEV infects neural stem/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, it is possible to reveal the impact of virus on the stem cells at protein level. Our aim was to perceive the stem cell proteomic response upon viral challenge. We performed a two-dimensional gel electrophoresis-based proteomic study of the human neural stem cells (hNS1 cell line) post JEV infection and found that 13 proteins were differentially expressed. The altered proteome profile of hNS1 cell line revealed sustained endoplasmic reticulum stress, which deteriorated normal cellular activities leading to cell apoptosis. The proteomic changes found in hNS1 cell line were validated
in vivo
in the subventricular zone of JE infected BALB/c mice. Congruent alterations were also witnessed in multipotent neural precursor cells isolated from human foetus and in autopsy samples of human brain clinically diagnosed as cases of JE patients. Endoplasmic reticulum resident chaperone GRP78, mitochondrial protein Prohibitin and heterogeneous nuclear ribonucleoprotein hnRNPC (C1/C2) have been shown to interact with viral RNA. Hence it is proposed that these are the principle candidates governing endoplasmic reticulum stress-induced apoptosis in JEV infection.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 82/51
/ 82/58
/ Animals
/ Biomedical and Life Sciences
/ Cell Proliferation - genetics
/ Electrophoresis, Gel, Two-Dimensional
/ Encephalitis Virus, Japanese - genetics
/ Encephalitis Virus, Japanese - pathogenicity
/ Encephalitis, Japanese - genetics
/ Encephalitis, Japanese - virology
/ Endoplasmic Reticulum Stress - genetics
/ Heat-Shock Proteins - biosynthesis
/ Heat-Shock Proteins - genetics
/ Heterogeneous-Nuclear Ribonucleoprotein Group C - biosynthesis
/ Heterogeneous-Nuclear Ribonucleoprotein Group C - genetics
/ Humans
/ Mice
/ Original
/ Repressor Proteins - biosynthesis
/ Repressor Proteins - genetics
/ Virology
