{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:46:33Z","timestamp":1791899193768,"version":"4.3.4"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T00:00:00Z","timestamp":1389744000000},"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":[[2014,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Though the compromised blood-brain barrier (BBB) is a pathological hallmark of Japanese encephalitis-associated neurological sequelae, the underlying mechanisms and the specific cell types involved are not understood. BBB characteristics are induced and maintained by cross talk between brain microvascular endothelial cells and neighboring elements of the neurovascular unit. In this study, we show a potential mechanism of disruption of endothelial barrier integrity during the course of Japanese encephalitis virus (JEV) infection through the activation of neighboring pericytes. We found that cultured brain pericytes were susceptible to JEV infection but were without signs of remarkable cytotoxicity. JEV-infected pericytes were found to release biologically active molecules which activated ubiquitin proteasome, degraded zonula occludens-1 (ZO-1), and disrupted endothelial barrier integrity in cultured brain microvascular endothelial cells. Infection of pericytes with JEV was found to elicit elevated production of interleukin-6 (IL-6), which contributed to the aforementioned endothelial changes. We further demonstrated that ubiquitin-protein ligase E3 component\n            <jats:italic>n<\/jats:italic>\n            -recognin-1 (Ubr 1) was a key upstream regulator which caused proteasomal degradation of ZO-1 downstream of IL-6 signaling. During JEV central nervous system trafficking, endothelial cells rather than pericytes are directly exposed to cell-free viruses in the peripheral bloodstream. Therefore, the results of this study suggest that subsequent to primary infection of endothelial cells, JEV infection of pericytes might contribute to the initiation and\/or augmentation of Japanese encephalitis-associated BBB breakdown in concerted action with other unidentified barrier disrupting factors.\n          <\/jats:p>","DOI":"10.1128\/jvi.02738-13","type":"journal-article","created":{"date-parts":[[2013,11,7]],"date-time":"2013-11-07T02:53:07Z","timestamp":1383792787000},"page":"1150-1161","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":108,"title":["Infection of Pericytes\n            <i>In Vitro<\/i>\n            by Japanese Encephalitis Virus Disrupts the Integrity of the Endothelial Barrier"],"prefix":"10.1128","volume":"88","author":[{"given":"Chun-Jung","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan"},{"name":"Center for General Education, Tunghai University, Taichung, Taiwan"},{"name":"Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan"},{"name":"Graduate School of Nursing, HungKuang University, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chuan","family":"Ou","sequence":"additional","affiliation":[{"name":"Division of Urology, Taichung Veterans General Hospital, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ri","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Urology, Taichung Veterans General Hospital, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Fong-Yuan Hospital, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Chuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yi","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Lan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shue-Ling","family":"Raung","sequence":"additional","affiliation":[{"name":"Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Jung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Sciences and Technology, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-006-9025-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000205"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-72-4-859"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05032-11"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.10.6291-6298.1994"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00710-07"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.44.100190.003245"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.4.405"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2006.02.008"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20474"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9071(199702)51:2<132::AID-JMV8>3.0.CO;2-8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/423328"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.06.015"},{"key":"e_1_3_2_16_2","first-page":"603","article-title":"Breakdown of blood-brain barrier by virus-induced cytokine during Japanese encephalitis virus infection","volume":"73","author":"Mathur A","year":"1992","unstructured":"MathurAKhannaNChaturvediUC. 1992. 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