{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:57:21Z","timestamp":1790783841313,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Japanese encephalitis virus (JEV) is an enveloped flavivirus with a single-stranded, positive-sense RNA genome encoding three structural and seven nonstructural proteins. To date, the role of JEV nonstructural protein 2A (NS2A) in the viral life cycle is largely unknown. The interferon (IFN)-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) phosphorylates the eukaryotic translation initiation factor 2\u03b1 subunit (eIF2\u03b1) after sensing viral RNA and results in global translation arrest as an important host antiviral defense response. In this study, we found that JEV NS2A could antagonize PKR-mediated growth inhibition in a galactose-inducible PKR-expressing yeast system. In human cells, PKR activation, eIF2\u03b1 phosphorylation, and the subsequent translational inhibition and cell death triggered by dsRNA and IFN-\u03b1 were also repressed by JEV NS2A. Moreover, among the four eIF2\u03b1 kinases, NS2A specifically blocked the eIF2\u03b1 phosphorylation mediated by PKR and attenuated the PKR-promoted cell death induced by the chemotherapeutic drug doxorubicin. A single point mutation of NS2A residue 33 from Thr to Ile (T33I) abolished the anti-PKR potential of JEV NS2A. The recombinant JEV mutant carrying the NS2A-T33I mutation showed reduced\n            <jats:italic>in vitro<\/jats:italic>\n            growth and\n            <jats:italic>in vivo<\/jats:italic>\n            virulence phenotypes. Thus, JEV NS2A has a novel function in blocking the host antiviral response of PKR during JEV infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.00525-12","type":"journal-article","created":{"date-parts":[[2012,7,12]],"date-time":"2012-07-12T04:53:58Z","timestamp":1342068838000},"page":"10347-10358","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":103,"title":["Blocking Double-Stranded RNA-Activated Protein Kinase PKR by Japanese Encephalitis Virus Nonstructural Protein 2A"],"prefix":"10.1128","volume":"86","author":[{"given":"Yu-Chun","family":"Tu","sequence":"first","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan"},{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yi","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Jong","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elong","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan"},{"name":"Department of Food Science and Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Len","family":"Liao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan"},{"name":"Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan"},{"name":"Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan"},{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan"},{"name":"Genomics Research Center, Academia Sinica, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002289"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010575"},{"key":"e_1_3_2_4_2","first-page":"277","article-title":"PKR in innate immunity, cancer, and viral oncolysis","volume":"383","author":"Balachandran S","year":"2007","unstructured":"BalachandranS BarberGN. 2007. 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