title: The NS3 protease and helicase domains of Japanese encephalitis virus             trigger cell death via caspase‑dependent and ‑independent pathways.
abstract: Japanese encephalitis virus (JEV), a mosquito‑borne flavivirus, causes acute             encephalitis and nervous damage. Previous studies have demonstrated that JEV induces             apoptosis in infected cells. However, to date the mechanisms of JEV‑induced apoptosis             are unclear. In order to identify the viral proteins associated with JEV‑induced             apoptosis, pEGFP‑non‑structural protein 3 (NS3) 1‑619 (expressing the JEV NS3             intact protein, including the protease and helicase domains), pEGFP‑NS3 1‑180             (expressing the protease domain) and pEGFP‑NS3 163‑619 (expressing the helicase             domain) were transfected into target cells to study cell death. Results demonstrate             that the JEV NS3 intact protein and protease and helicase domains induce cell             death. In addition, cell death was identified to be significantly higher in cells             transfected with the NS3 protease domain compared with the intact protein and             helicase domain. Caspase activation was also analyzed in the current study. NS3             intact protein and NS3 protease and helicase domains activated caspase‑9/‑3‑dependent             and ‑independent pathways. However, caspase‑8 activity was not found to be significantly             different in NS3‑transfected cells compared with control. In summary, the present             study demonstrates that the NS3 helicase and protease domains of JEV activate             caspase‑9/‑3‑dependent and ‑independent cascades and trigger cell death.
authors.affiliation: Department of Emergency Medicine, Tzu Chi University, Hualien 970, Taiwan, ROC.
authors.forename: Giou-Teng
authors.initials: GT
authors.lastname: Yiang
authors.forename: Yen-Hsieh
authors.initials: YH
authors.lastname: Chen
authors.forename: Pei-Lun
authors.initials: PL
authors.lastname: Chou
authors.forename: Wei-Jung
authors.initials: WJ
authors.lastname: Chang
authors.forename: Chyou-Wei
authors.initials: CW
authors.lastname: Wei
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004664:Encephalitis Virus, Japanese / Q000201:enzymology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D004265:DNA Helicases; D049452:Green Fluorescent Proteins; D020365:RNA Helicases; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C485184:enhanced green fluorescent protein