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Group A rotaviruses produce extrahepatic biliary obstruction in orally inoculated newborn mice
M Riepenhoff-Talty1, K Schaekel, H F Clark
1Department of Pediatrics, School of Medicine, State University of New York, Buffalo.
Insights
Group A rotavirus infection in infant mice can cause extrahepatic biliary obstruction, mimicking human biliary atresia. This study establishes a new animal model for studying this severe infant liver disease.
Area of Science:
- Pediatric Hepatology
- Virology
- Animal Models
Background:
- Extrahepatic biliary atresia is a severe infant liver disease with an unknown cause.
- Previous research suggested a link between group C rotavirus and biliary atresia.
- Group A rotaviruses are known to cause hepatobiliary disease in infant mice.
Purpose of the Study:
- To investigate the potential of group A rotavirus to induce extrahepatic biliary obstruction in an animal model.
- To characterize the pathological changes in the liver and biliary tract following rotavirus infection in mice.
Main Methods:
- Infant BALB/c mice were orally inoculated with human or animal strains of group A rotavirus.
- Virus replication in the liver and biliary tract was assessed.
- Histopathological examination of bile ducts and liver was performed to identify signs of inflammation, swelling, and obstruction.
Main Results:
- Active rotavirus replication was observed in the biliary tract and liver within 48 hours post-inoculation.
- Between 25% and 50% of infected mice developed inflammation and swelling of the bile ducts.
- Approximately 50% of symptomatic mice experienced complete bile duct obstruction, which was irreversible in about half of these cases.
- Fibrosis and bile ductular proliferation in the liver were noted, resembling changes seen in human biliary atresia.
Conclusions:
- Group A rotavirus infection can lead to extrahepatic biliary obstruction in infant mice.
- This model exhibits key pathological features similar to human biliary atresia, providing a valuable tool for further research.
- The findings suggest a potential role for group A rotavirus in the pathogenesis of biliary atresia.
Abstract:
Extrahepatic biliary atresia is a devastating disease occurring in 1 in 10,000 to 14,000 infants annually in the United States. We have recently described preliminary data suggesting an association of group C rotavirus with biliary atresia in two infants. However, a group C rotavirus animal model of biliary atresia is not presently available. On the other hand, some strains of the better-characterized and much more common group A rotaviruses produce hepatobiliary disease in infant mice. This disease shares many characteristics of the human infection. The present report describes extrahepatic biliary obstruction in immunocompetent BALB/c infant mice infected with a human or animal strain of group A rotavirus. Two-d-old BALB/c mice orally inoculated with hepatobiliary tropic rotavirus were shown to have active virus replication in the biliary tract and liver as early as 48 h postinoculation. At approximately 7 d postinoculation, between one fourth and one half of infant mice, depending on the virus strain, showed signs of inflammation and swelling in the bile ducts. The obstruction was complete in about one half of symptomatic animals. Although there was no obvious atresia as described in human infants, the obstruction was irreversible about 50% of the time, and the resulting fibrosis and bile ductular proliferation in the liver were strikingly similar to those seen in the liver of the human infant with biliary atresia.