title: Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress.
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.
authors.affiliation: National Brain Research Centre, Manesar 122051, Haryana, India.|Immunology Lab, Department of Zoology, University of Calcutta, 35, Ballygange Circular Road, Kolkata 700019, India.
authors.forename: Sriparna
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: National Brain Research Centre, Manesar 122051, Haryana, India.
authors.forename: Noopur
authors.initials: N
authors.lastname: Singh
authors.affiliation: National Brain Research Centre, Manesar 122051, Haryana, India.
authors.forename: Nabonita
authors.initials: N
authors.lastname: Sengupta
authors.affiliation: National Brain Research Centre, Manesar 122051, Haryana, India.
authors.forename: Mahar
authors.initials: M
authors.lastname: Fatima
authors.affiliation: National Brain Research Centre, Manesar 122051, Haryana, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.affiliation: Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore 560029, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Mahadevan
authors.affiliation: Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore 560029, India.
authors.forename: Susarla Krishna
authors.initials: SK
authors.lastname: Shankar
authors.affiliation: Immunology Lab, Department of Zoology, University of Calcutta, 35, Ballygange Circular Road, Kolkata 700019, India.
authors.forename: Arindam
authors.initials: A
authors.lastname: Bhattacharyya
authors.affiliation: National Brain Research Centre, Manesar 122051, Haryana, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000472:pathogenicity; D004672:Encephalitis, Japanese / Q000235:genetics* / Q000821:virology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D000091402:Prohibitins; D020543:Proteome / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C503635:HNRNPC protein, human; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; C000717248:Hspa5 protein, mouse; C000717328:PHB protein, human; D000091402:Prohibitins; D020543:Proteome; D012367:RNA, Viral; D012097:Repressor Proteins