Rotavirus reassortant induced murine model of liver fibrosis
AbstractBiliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end‐stage liver disease by two years of age. Portoenterostomy may re‐establish biliary drainage but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end stage liver disease requiring liver transplantation for survival. 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 a novel 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. This novel 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 novel therapeutic targets that may alter the course of BA.
https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.30907
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