Mukherjee, Sriparna and Singh, Noopur and Sengupta, Nabonita and Fatima, Mahar and Seth, Pankaj and Mahadevan, Anita and Shankar, Susarla Krishna and Bhattacharyya, Arindam and Basu, Anirban (2017) Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress. In: Cell Death & Disease, 8 (1). ISSN 2041-4889
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Abstract
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.
| Item Type: | Journal Article |
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| Publication: | Cell Death & Disease |
| Publisher: | Nature Publishing Group |
| Additional Information: | The Copyright of this article belongs to the Authors |
| Keywords: | Animals; Apoptosis; Cell Proliferation; Electrophoresis, Gel, Two-Dimensional; Encephalitis Virus, Japanese; Encephalitis, Japanese; Endoplasmic Reticulum Stress; Gene Expression Regulation; Heat-Shock Proteins; Heterogeneous-Nuclear Ribonucleoprotein Group C; Humans; Mice; Proteome; Repressor Proteins; RNA, Viral; activating transcription factor 6; calreticulin; caspase; caspase 3; chaperone; cytochrome c; gamma interferon; glucose regulated protein 78; heterogeneous nuclear ribonucleoprotein; hyou1 protein; interleukin 12; interleukin 1beta; interleukin 6; interleukin 8; monocyte chemotactic protein 1; prohibitin; protein; protein IRE1; reactive oxygen metabolite; tumor necrosis factor; unclassified drug; vimentin; X linked inhibitor of apoptosis; heat shock protein; heterogeneous nuclear ribonucleoprotein group C; HNRNPC protein, human; molecular chaperone GRP78; prohibitin; proteome; repressor protein; virus RNA; animal cell; apoptosis; Article; autopsy; basal ganglion; cell death; controlled study; cytopathogenic effect; down regulation; encephalitis; endoplasmic reticulum stress; enzyme activation; fetus; fluorescence activated cell sorting; human; human cell; immunoblotting; immunocytochemistry; immunofluorescence test; immunohistochemistry; Japanese encephalitis virus; mass spectrometry; mouse; neural stem cell; nonhuman; plaque assay; priority journal; protein expression; protein RNA binding; protein transport; proteomics; real time polymerase chain reaction; subventricular zone; TUNEL assay; two dimensional gel electrophoresis; upregulation; validation study; virus infection; virus load; virus particle; virus replication; animal; biosynthesis; cell proliferation; endoplasmic reticulum stress; gene expression regulation; genetics; Japanese encephalitis; Japanese encephalitis virus; pathogenicity; virology |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 05 Jun 2022 05:27 |
| Last Modified: | 05 Jun 2022 05:27 |
| URI: | https://eprints.iisc.ac.in/id/eprint/72954 |
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