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This study characterizes Type I IFN<\/jats:styled-content> antagonism mechanism of NS<\/jats:styled-content>5 protein, using proteomic approach. In human neuroblastoma cells, NS<\/jats:styled-content>5 expression would suppress IFN<\/jats:styled-content>\u03b2\u2010induced responses, for example, expression of IFN<\/jats:styled-content>\u2010stimulated genes PKR<\/jats:styled-content> and OAS<\/jats:styled-content> as well as STAT<\/jats:styled-content>1 nuclear translocation and phosphorylation. Proteomic analysis showed JEV NS<\/jats:styled-content>5 downregulating calreticulin, while upregulating cyclophilin A<\/jats:styled-content>, HSP<\/jats:styled-content> 60 and stress\u2010induced\u2010phosphoprotein 1. Gene silence of calreticulin raised intracellular C<\/jats:styled-content>a2+<\/jats:sup> levels while inhibiting nuclear translocalization of STAT<\/jats:styled-content>1 and NFAT<\/jats:styled-content>\u20101 in response to IFN<\/jats:styled-content>\u03b2, thus, indicating calreticulin downregulation linked with T<\/jats:styled-content>ype I IFN<\/jats:styled-content> antagonism of JEV NS<\/jats:styled-content>5 via activation of Ca2+<\/jats:sup>\/calicineurin. Calcineurin inhibitor cyclosporin A attenuated NS5\u2010mediated inhibition of IFN<\/jats:styled-content>\u03b2\u2010induced responses, for example, IFN<\/jats:styled-content>\u2010sensitive response element driven luciferase, STAT<\/jats:styled-content>1\u2010dependent PKR<\/jats:styled-content> mRNA<\/jats:styled-content> expression, as well as phosphorylation and nuclear translocation of STAT<\/jats:styled-content>1. Transfection with calcineurin (vs. control) siRNA<\/jats:styled-content> enhanced nuclear translocalization of STAT<\/jats:styled-content>1 and upregulated PKR<\/jats:styled-content> expression in NS<\/jats:styled-content>5\u2010expressing cells in response to IFN<\/jats:styled-content>\u03b2. Results prove C<\/jats:styled-content>a2+<\/jats:sup>, calreticulin, and calcineurin involvement in STAT<\/jats:styled-content>1\u2010mediated signaling as well as a key role of JEV NS<\/jats:styled-content>5 in T<\/jats:styled-content>ype I IFN<\/jats:styled-content> antagonism. This study offers insights into the molecular mechanism of T<\/jats:styled-content>ype I<\/jats:styled-content> interferon antagonism by JEV NS<\/jats:styled-content>5.<\/jats:p>","DOI":"10.1002\/pmic.201300001","type":"journal-article","created":{"date-parts":[[2013,10,24]],"date-time":"2013-10-24T10:36:58Z","timestamp":1382611018000},"page":"3442-3456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Proteomic analysis for T<\/scp>ype I<\/scp> interferon antagonism of J<\/scp>apanese encephalitis virus NS<\/scp>5 protein"],"prefix":"10.1002","volume":"13","author":[{"given":"Tsuey\u2010Ching","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Laboratory Science in Medicine National Yang Ming University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Wein","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien\u2010Chen","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Medical Research China Medical University Hospital Taichung Taiwan"},{"name":"Institute of Molecular Biology National Chung Hsing University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Zen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u2010Tzu","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung\u2010Han","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Medical Research China Medical University Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology China Medical University Taichung Taiwan"},{"name":"Department of Biotechnology College of Health Science Asia University, Wufeng Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,2]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1043","volume-title":"Fields Virology","author":"Burke D. 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