{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:17:03Z","timestamp":1793060223150,"version":"4.5.0"},"reference-count":71,"publisher":"American Society for Microbiology","issue":"23","license":[{"start":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T00:00:00Z","timestamp":1164931200000},"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":[[2006,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The unfolded protein response (UPR) is a coordinated change in gene expression triggered by perturbations in functions of the endoplasmic reticulum (ER). XBP1, a key transcription factor of the UPR, is activated by an IRE1-mediated splicing event, which results in a frameshift and encodes a protein with transcriptional activity. Here, we report that XBP1 was activated during flaviviral infection, as evidenced by\n            <jats:italic>XBP1<\/jats:italic>\n            mRNA splicing and protein expression, as well as induction of the downstream genes\n            <jats:italic>ERdj4<\/jats:italic>\n            ,\n            <jats:italic>EDEM1<\/jats:italic>\n            , and\n            <jats:italic>p58(IPK)<\/jats:italic>\n            in Japanese encephalitis virus (JEV)- and dengue virus serotype 2 (DEN-2)-infected cells. Reporter systems based on IRE1-mediated\n            <jats:italic>XBP1<\/jats:italic>\n            splicing were established, and several flaviviral proteins associated with the ER, including glycoproteins and small hydrophobic membrane-anchored proteins, were found to trigger the splicing event. Notably, nonstructural protein NS2B-3 of DEN-2, but not of JEV, was a potent inducer of\n            <jats:italic>XBP1<\/jats:italic>\n            splicing through an unclear mechanism(s). Reduction of XBP1 by a small interfering RNA had no effect on cells' susceptibility to the two viruses but exacerbated the flavivirus-induced cytopathic effects. Overall, flaviviruses trigger the XBP1 signaling pathway and take advantage of this cellular response to alleviate virus-induced cytotoxicity.\n          <\/jats:p>","DOI":"10.1128\/jvi.00879-06","type":"journal-article","created":{"date-parts":[[2006,11,13]],"date-time":"2006-11-13T19:03:38Z","timestamp":1163444618000},"page":"11868-11880","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":236,"title":["Flavivirus Infection Activates the XBP1 Pathway of the Unfolded Protein Response To Cope with Endoplasmic Reticulum Stress"],"prefix":"10.1128","volume":"80","author":[{"given":"Chia-Yi","family":"Yu","sequence":"first","affiliation":[{"name":"Graduate Institute of Life Sciences"},{"name":"Institute of Biomedical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Defense Medical Center"},{"name":"Institute of Biomedical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Len","family":"Liao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences"},{"name":"Department of Microbiology and Immunology, National Defense Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences"},{"name":"Institute of Biomedical Sciences"},{"name":"Genomics Research Center, Academia Sinica, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.1.258"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208673"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35014014"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401817"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068999"},{"key":"e_1_3_2_7_2","first-page":"1043","volume":"1","year":"2001","unstructured":"Burke, D. 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