Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia

Sujit K. Mohanty*, Inna Lobeck, Bryan Donnelly, Phylicia Dupree, Ashley Walther, Sarah Mowery, Abigail Coots, Alexander Bondoc, Rachel M. Sheridan, Holly M. Poling, Haley Temple, Monica McNeal, Karol Sestak, Ruchi Bansal, Greg Tiao

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1316-1330
Number of pages15
JournalHepatology
Volume71
Issue number4
DOIs
Publication statusPublished - 1 Apr 2020

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