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Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia
Author(s) -
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
Publication year - 2020
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30907
Subject(s) - biliary atresia , medicine , fibrosis , liver transplantation , liver disease , rotavirus , gastroenterology , jaundice , disease , immunology , transplantation , pathology , virus
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 T R(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.