{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:24:34Z","timestamp":1778905474476,"version":"3.51.4"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Biliary atresia (BA) is a neonatal inflammatory cholangiopathy that requires surgical intervention by Kasai portoenterostomy to restore biliary drainage. Even with successful portoenterostomy, most patients diagnosed with BA progress to end\u2010stage liver disease, necessitating a liver transplantation for survival. In the murine model of BA, rhesus rotavirus (RRV) infection of neonatal mice induces an inflammatory obstructive cholangiopathy that parallels human BA. The model is triggered by RRV viral protein (VP)4 binding to cholangiocyte cell\u2010surface proteins. High mobility group box 1 (HMGB1) protein is a danger\u2010associated molecular pattern that when released extracellularly moderates innate and adaptive immune response. In this study, we investigated how mutations in three RRV VP4\u2010binding sites, RRV<jats:sup>VP4\u2010K187R<\/jats:sup> (sialic acid\u2010binding site), RRV<jats:sup>VP4\u2010D308A<\/jats:sup> (integrin \u03b12\u03b21\u2010binding site), and RRV<jats:sup>VP4\u2010R446G<\/jats:sup> (heat shock cognate 70 [Hsc70]\u2010binding site), affects infection, HMGB1 release, and the murine model of BA. Newborn pups injected with RRV<jats:sup>VP4\u2010K187R<\/jats:sup> and RRV<jats:sup>VP4\u2010D308A<\/jats:sup> developed an obstruction within the extrahepatic bile duct similar to wild\u2010type RRV, while those infected with RRV<jats:sup>VP4\u2010R446G<\/jats:sup> remained patent. Infection with RRV<jats:sup>VP4\u2010R446G<\/jats:sup> induced a lower level of HMGB1 release from cholangiocytes and in the serum of infected pups. RRV infection of HeLa cells lacking Hsc70 resulted in no HMGB1 release, while transfection with wild\u2010type Hsc70 into HeLa Hsc70\u2010deficient cells reestablished HMGB1 release, indicating a mechanistic role for Hsc70 in its release. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Binding to Hsc70 contributes to HMGB1 release; therefore, Hsc70 potentially serves as a therapeutic target for BA.<\/jats:p>","DOI":"10.1002\/hep4.2024","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T11:14:20Z","timestamp":1658488460000},"page":"2702-2714","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Rhesus rotavirus receptor\u2010binding site affects high mobility group box 1 release, altering the pathogenesis of\u00a0experimental biliary atresia"],"prefix":"10.1097","volume":"6","author":[{"given":"Sujit K.","family":"Mohanty","sequence":"first","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley","family":"Temple","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Mowery","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly\u00a0M.","family":"Poling","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaroslaw","family":"Meller","sequence":"additional","affiliation":[{"name":"Department of Environmental and Public Health Sciences,University of Cincinnati,Cincinnati,Ohio,USA"},{"name":"Division of Biomedical Informatics,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astha","family":"Malik","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Cincinnati Children's Hospital Medical 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