The NS3 protease and helicase domains of Japanese encephalitis virus trigger cell death via caspase‑dependent and ‑independent pathways

Yiang,Giou‑Teng; Chen,Yen‑Hsieh; Chou,Pei‑Lun; Chang,Wei‑Jung; Wei,Chyou‑Wei; Yu,Yung‑Luen

doi:10.3892/mmr.2013.1261

The NS3 protease and helicase domains of Japanese encephalitis virus trigger cell death via caspase‑dependent and ‑independent pathways

Authors:
- Giou‑Teng Yiang
- Yen‑Hsieh Chen
- Pei‑Lun Chou
- Wei‑Jung Chang
- Chyou‑Wei Wei
- Yung‑Luen Yu
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Affiliations: Department of Emergency Medicine, Tzu Chi University, Hualien 970, Taiwan, R.O.C., Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan, R.O.C., Department of Internal Medicine, Division of Allergy‑Immunology‑Rheumatology, Saint Mary's Hospital, Luodong 265, Taiwan, R.O.C., Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C., Graduate Institute of Cancer Biology, China Medical University, 6 Hsueh‑Shih Road Taichung 404, Taiwan, R.O.C.
Published online on: January 3, 2013 https://doi.org/10.3892/mmr.2013.1261
Pages: 826-830

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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.

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