Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia
Background and Aims Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end‐stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end...
Gespeichert in:
| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2020-04, Vol.71 (4), p.1316-1330 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1330 |
|---|---|
| container_issue | 4 |
| container_start_page | 1316 |
| container_title | Hepatology (Baltimore, Md.) |
| container_volume | 71 |
| creator | Mohanty, Sujit K. Lobeck, Inna Donnelly, Bryan Dupree, Phylicia Walther, Ashley Mowery, Sarah Coots, Abigail Bondoc, Alexander Sheridan, Rachel M. Poling, Holly M. Temple, Haley McNeal, Monica Sestak, Karol Bansal, Ruchi Tiao, Greg |
| description | Background and Aims
Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end‐stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end‐stage liver disease requiring liver transplantation for survival.
Approach and Results
In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling human BA and has been used to study mechanistic aspects of the disease. Unfortunately, nearly all RRV‐infected pups succumb by day of life 14. Thus, in this study we generated an RRV‐TUCH rotavirus reassortant (designated as TR(VP2,VP4)) that when injected into newborn mice causes an obstructive jaundice phenotype with lower mortality rates. Of the mice that survived, 63% developed Ishak stage 3‐5 fibrosis with histopathological signs of inflammation/fibrosis and bile duct obstruction.
Conclusions
This model of rotavirus‐induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies with an objective to identify therapeutic targets that may alter the course of BA. |
| doi_str_mv | 10.1002/hep.30907 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7384231</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2313358540</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4437-5ca2358b1f090ac8eb1d79c124a41c2d4409e7d0f53cdc2304f4297b609204523</originalsourceid><addsrcrecordid>eNp1kc9O3DAQh62qVVmgh75AZamX9pBl_CckuSBtEbBIi4oQXLEcZwJG3nixk6248Q68IU-CtwuIIvU0h_n06TfzI-QrgzED4DvXuBgLqKD4QEYs50UmRA4fyQh4AVnFRLVBNmO8AYBK8vIz2RBMSi44H5HLM9_rpQ1DpGeoY_Sh113_eP9w3DWDwYaeDMF2SE98g476ls7sEgM9tHXw0UZ6qoN2Dl2k02GuO_rLOqvDHZ30AaPV2-RTq13EL89zi1wcHpzvT7PZ76Pj_cksM1KKIsuN5iIva9amK7QpsWZNURnGpZbM8EZKqLBooM2FaQwXIFvJq6LehYqDzLnYIntr72Ko59gY7PqUSy2Cnac0ymur_t109lpd-aUqRJk-wZLgx7Mg-NsBY6_mNhp0Tnfoh6hWTEqYS0jo93fojR9Cl85LVFlCyRmIRP1cUyY9KgZsX8MwUKvWVGpN_W0tsd_epn8lX2pKwM4a-GMd3v3fpKYHp2vlEwVVog4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2388082103</pqid></control><display><type>article</type><title>Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Mohanty, Sujit K. ; Lobeck, Inna ; Donnelly, Bryan ; Dupree, Phylicia ; Walther, Ashley ; Mowery, Sarah ; Coots, Abigail ; Bondoc, Alexander ; Sheridan, Rachel M. ; Poling, Holly M. ; Temple, Haley ; McNeal, Monica ; Sestak, Karol ; Bansal, Ruchi ; Tiao, Greg</creator><creatorcontrib>Mohanty, Sujit K. ; Lobeck, Inna ; Donnelly, Bryan ; Dupree, Phylicia ; Walther, Ashley ; Mowery, Sarah ; Coots, Abigail ; Bondoc, Alexander ; Sheridan, Rachel M. ; Poling, Holly M. ; Temple, Haley ; McNeal, Monica ; Sestak, Karol ; Bansal, Ruchi ; Tiao, Greg</creatorcontrib><description>Background and Aims
Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end‐stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end‐stage liver disease requiring liver transplantation for survival.
Approach and Results
In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling human BA and has been used to study mechanistic aspects of the disease. Unfortunately, nearly all RRV‐infected pups succumb by day of life 14. Thus, in this study we generated an RRV‐TUCH rotavirus reassortant (designated as TR(VP2,VP4)) that when injected into newborn mice causes an obstructive jaundice phenotype with lower mortality rates. Of the mice that survived, 63% developed Ishak stage 3‐5 fibrosis with histopathological signs of inflammation/fibrosis and bile duct obstruction.
Conclusions
This model of rotavirus‐induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies with an objective to identify therapeutic targets that may alter the course of BA.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.30907</identifier><identifier>PMID: 31442322</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health, Inc</publisher><subject>Animal models ; Animals ; Bile ; Bile ducts ; Biliary atresia ; Biliary Atresia - complications ; Cell Line ; Chlorocebus aethiops ; Disease Models, Animal ; Fibrosis ; Hepatology ; Humans ; Jaundice ; Jaundice, Obstructive - virology ; Juveniles ; Liver Cirrhosis - etiology ; Liver Cirrhosis - virology ; Liver diseases ; Liver transplantation ; Mice ; Mice, Inbred BALB C ; Neonates ; Original ; Phenotypes ; Reassortant Viruses ; Rotavirus ; Therapeutic applications ; Viruses ; Wound drainage</subject><ispartof>Hepatology (Baltimore, Md.), 2020-04, Vol.71 (4), p.1316-1330</ispartof><rights>2019 The Authors. H published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.</rights><rights>2019 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.</rights><rights>2019. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4437-5ca2358b1f090ac8eb1d79c124a41c2d4409e7d0f53cdc2304f4297b609204523</citedby><cites>FETCH-LOGICAL-c4437-5ca2358b1f090ac8eb1d79c124a41c2d4409e7d0f53cdc2304f4297b609204523</cites><orcidid>0000-0002-8603-2876</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.30907$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.30907$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31442322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohanty, Sujit K.</creatorcontrib><creatorcontrib>Lobeck, Inna</creatorcontrib><creatorcontrib>Donnelly, Bryan</creatorcontrib><creatorcontrib>Dupree, Phylicia</creatorcontrib><creatorcontrib>Walther, Ashley</creatorcontrib><creatorcontrib>Mowery, Sarah</creatorcontrib><creatorcontrib>Coots, Abigail</creatorcontrib><creatorcontrib>Bondoc, Alexander</creatorcontrib><creatorcontrib>Sheridan, Rachel M.</creatorcontrib><creatorcontrib>Poling, Holly M.</creatorcontrib><creatorcontrib>Temple, Haley</creatorcontrib><creatorcontrib>McNeal, Monica</creatorcontrib><creatorcontrib>Sestak, Karol</creatorcontrib><creatorcontrib>Bansal, Ruchi</creatorcontrib><creatorcontrib>Tiao, Greg</creatorcontrib><title>Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Background and Aims
Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end‐stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end‐stage liver disease requiring liver transplantation for survival.
Approach and Results
In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling human BA and has been used to study mechanistic aspects of the disease. Unfortunately, nearly all RRV‐infected pups succumb by day of life 14. Thus, in this study we generated an RRV‐TUCH rotavirus reassortant (designated as TR(VP2,VP4)) that when injected into newborn mice causes an obstructive jaundice phenotype with lower mortality rates. Of the mice that survived, 63% developed Ishak stage 3‐5 fibrosis with histopathological signs of inflammation/fibrosis and bile duct obstruction.
Conclusions
This model of rotavirus‐induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies with an objective to identify therapeutic targets that may alter the course of BA.</description><subject>Animal models</subject><subject>Animals</subject><subject>Bile</subject><subject>Bile ducts</subject><subject>Biliary atresia</subject><subject>Biliary Atresia - complications</subject><subject>Cell Line</subject><subject>Chlorocebus aethiops</subject><subject>Disease Models, Animal</subject><subject>Fibrosis</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Jaundice</subject><subject>Jaundice, Obstructive - virology</subject><subject>Juveniles</subject><subject>Liver Cirrhosis - etiology</subject><subject>Liver Cirrhosis - virology</subject><subject>Liver diseases</subject><subject>Liver transplantation</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neonates</subject><subject>Original</subject><subject>Phenotypes</subject><subject>Reassortant Viruses</subject><subject>Rotavirus</subject><subject>Therapeutic applications</subject><subject>Viruses</subject><subject>Wound drainage</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc9O3DAQh62qVVmgh75AZamX9pBl_CckuSBtEbBIi4oQXLEcZwJG3nixk6248Q68IU-CtwuIIvU0h_n06TfzI-QrgzED4DvXuBgLqKD4QEYs50UmRA4fyQh4AVnFRLVBNmO8AYBK8vIz2RBMSi44H5HLM9_rpQ1DpGeoY_Sh113_eP9w3DWDwYaeDMF2SE98g476ls7sEgM9tHXw0UZ6qoN2Dl2k02GuO_rLOqvDHZ30AaPV2-RTq13EL89zi1wcHpzvT7PZ76Pj_cksM1KKIsuN5iIva9amK7QpsWZNURnGpZbM8EZKqLBooM2FaQwXIFvJq6LehYqDzLnYIntr72Ko59gY7PqUSy2Cnac0ymur_t109lpd-aUqRJk-wZLgx7Mg-NsBY6_mNhp0Tnfoh6hWTEqYS0jo93fojR9Cl85LVFlCyRmIRP1cUyY9KgZsX8MwUKvWVGpN_W0tsd_epn8lX2pKwM4a-GMd3v3fpKYHp2vlEwVVog4</recordid><startdate>202004</startdate><enddate>202004</enddate><creator>Mohanty, Sujit K.</creator><creator>Lobeck, Inna</creator><creator>Donnelly, Bryan</creator><creator>Dupree, Phylicia</creator><creator>Walther, Ashley</creator><creator>Mowery, Sarah</creator><creator>Coots, Abigail</creator><creator>Bondoc, Alexander</creator><creator>Sheridan, Rachel M.</creator><creator>Poling, Holly M.</creator><creator>Temple, Haley</creator><creator>McNeal, Monica</creator><creator>Sestak, Karol</creator><creator>Bansal, Ruchi</creator><creator>Tiao, Greg</creator><general>Wolters Kluwer Health, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8603-2876</orcidid></search><sort><creationdate>202004</creationdate><title>Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia</title><author>Mohanty, Sujit K. ; Lobeck, Inna ; Donnelly, Bryan ; Dupree, Phylicia ; Walther, Ashley ; Mowery, Sarah ; Coots, Abigail ; Bondoc, Alexander ; Sheridan, Rachel M. ; Poling, Holly M. ; Temple, Haley ; McNeal, Monica ; Sestak, Karol ; Bansal, Ruchi ; Tiao, Greg</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4437-5ca2358b1f090ac8eb1d79c124a41c2d4409e7d0f53cdc2304f4297b609204523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Bile</topic><topic>Bile ducts</topic><topic>Biliary atresia</topic><topic>Biliary Atresia - complications</topic><topic>Cell Line</topic><topic>Chlorocebus aethiops</topic><topic>Disease Models, Animal</topic><topic>Fibrosis</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Jaundice</topic><topic>Jaundice, Obstructive - virology</topic><topic>Juveniles</topic><topic>Liver Cirrhosis - etiology</topic><topic>Liver Cirrhosis - virology</topic><topic>Liver diseases</topic><topic>Liver transplantation</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neonates</topic><topic>Original</topic><topic>Phenotypes</topic><topic>Reassortant Viruses</topic><topic>Rotavirus</topic><topic>Therapeutic applications</topic><topic>Viruses</topic><topic>Wound drainage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mohanty, Sujit K.</creatorcontrib><creatorcontrib>Lobeck, Inna</creatorcontrib><creatorcontrib>Donnelly, Bryan</creatorcontrib><creatorcontrib>Dupree, Phylicia</creatorcontrib><creatorcontrib>Walther, Ashley</creatorcontrib><creatorcontrib>Mowery, Sarah</creatorcontrib><creatorcontrib>Coots, Abigail</creatorcontrib><creatorcontrib>Bondoc, Alexander</creatorcontrib><creatorcontrib>Sheridan, Rachel M.</creatorcontrib><creatorcontrib>Poling, Holly M.</creatorcontrib><creatorcontrib>Temple, Haley</creatorcontrib><creatorcontrib>McNeal, Monica</creatorcontrib><creatorcontrib>Sestak, Karol</creatorcontrib><creatorcontrib>Bansal, Ruchi</creatorcontrib><creatorcontrib>Tiao, Greg</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mohanty, Sujit K.</au><au>Lobeck, Inna</au><au>Donnelly, Bryan</au><au>Dupree, Phylicia</au><au>Walther, Ashley</au><au>Mowery, Sarah</au><au>Coots, Abigail</au><au>Bondoc, Alexander</au><au>Sheridan, Rachel M.</au><au>Poling, Holly M.</au><au>Temple, Haley</au><au>McNeal, Monica</au><au>Sestak, Karol</au><au>Bansal, Ruchi</au><au>Tiao, Greg</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2020-04</date><risdate>2020</risdate><volume>71</volume><issue>4</issue><spage>1316</spage><epage>1330</epage><pages>1316-1330</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><abstract>Background and Aims
Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end‐stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end‐stage liver disease requiring liver transplantation for survival.
Approach and Results
In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling human BA and has been used to study mechanistic aspects of the disease. Unfortunately, nearly all RRV‐infected pups succumb by day of life 14. Thus, in this study we generated an RRV‐TUCH rotavirus reassortant (designated as TR(VP2,VP4)) that when injected into newborn mice causes an obstructive jaundice phenotype with lower mortality rates. Of the mice that survived, 63% developed Ishak stage 3‐5 fibrosis with histopathological signs of inflammation/fibrosis and bile duct obstruction.
Conclusions
This model of rotavirus‐induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies with an objective to identify therapeutic targets that may alter the course of BA.</abstract><cop>United States</cop><pub>Wolters Kluwer Health, Inc</pub><pmid>31442322</pmid><doi>10.1002/hep.30907</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-8603-2876</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0270-9139 |
| ispartof | Hepatology (Baltimore, Md.), 2020-04, Vol.71 (4), p.1316-1330 |
| issn | 0270-9139 1527-3350 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7384231 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animal models Animals Bile Bile ducts Biliary atresia Biliary Atresia - complications Cell Line Chlorocebus aethiops Disease Models, Animal Fibrosis Hepatology Humans Jaundice Jaundice, Obstructive - virology Juveniles Liver Cirrhosis - etiology Liver Cirrhosis - virology Liver diseases Liver transplantation Mice Mice, Inbred BALB C Neonates Original Phenotypes Reassortant Viruses Rotavirus Therapeutic applications Viruses Wound drainage |
| title | Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T23%3A38%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rotavirus%20Reassortant%E2%80%93Induced%20Murine%20Model%20of%20Liver%20Fibrosis%20Parallels%20Human%20Biliary%20Atresia&rft.jtitle=Hepatology%20(Baltimore,%20Md.)&rft.au=Mohanty,%20Sujit%20K.&rft.date=2020-04&rft.volume=71&rft.issue=4&rft.spage=1316&rft.epage=1330&rft.pages=1316-1330&rft.issn=0270-9139&rft.eissn=1527-3350&rft_id=info:doi/10.1002/hep.30907&rft_dat=%3Cproquest_pubme%3E2313358540%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2388082103&rft_id=info:pmid/31442322&rfr_iscdi=true |