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

Sujit K Mohanty1, Inna Lobeck1, Bryan Donnelly1

  • 1Department of Pediatric and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Hepatology (Baltimore, Md.)
|August 24, 2019
PubMed

Insights

A new rotavirus model in mice mimics biliary atresia (BA), a neonatal liver disease. This model shows promise for studying BA pathogenesis and developing new therapies to combat liver fibrosis.

Area of Science:

  • Hepatology
  • Pediatric Gastroenterology
  • Virology

Background:

  • Biliary atresia (BA) is a severe neonatal liver disease leading to fibrosis and end-stage liver disease within two years.
  • Current treatments like portoenterostomy often fail to prevent disease progression, necessitating liver transplantation.

Purpose of the Study:

  • To develop a more viable murine model of biliary atresia (BA) for studying disease mechanisms.
  • To create a model that allows for investigation into therapeutic targets for neonatal liver fibrosis.

Main Methods:

  • Generated a novel rhesus rotavirus (RRV)-TUCH reassortant (TR(VP2,VP4)) for infection in newborn mice.
  • Administered the reassortant to newborn mice to induce a cholestatic liver injury model.

Main Results:

  • The modified rotavirus caused obstructive jaundice with reduced mortality compared to wild-type RRV.
  • In surviving mice, 63% developed significant liver fibrosis (Ishak stage 3-5) with inflammation and bile duct obstruction.

Conclusions:

  • The developed rotavirus-induced neonatal fibrosis model effectively mimics key aspects of human biliary atresia.
  • This model offers a valuable platform for preclinical studies to identify therapeutic strategies for biliary atresia and related liver fibrosis.
Abstract

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