Utilization of sialic acid as a coreceptor is required for reovirus-induced biliary disease

J Clin Invest. 2003 Jun;111(12):1823-33. doi: 10.1172/JCI16303.


Infection of neonatal mice with some reovirus strains produces a disease similar to infantile biliary atresia, but previous attempts to correlate reovirus infection with this disease have yielded conflicting results. We used isogenic reovirus strains T3SA- and T3SA+, which differ solely in the capacity to bind sialic acid as a coreceptor, to define the role of sialic acid in reovirus encephalitis and biliary tract infection in mice. Growth in the intestine was equivalent for both strains following peroral inoculation. However, T3SA+ spread more rapidly from the intestine to distant sites and replicated to higher titers in spleen, liver, and brain. Strikingly, mice infected with T3SA+ but not T3SA- developed steatorrhea and bilirubinemia. Liver tissue from mice infected with T3SA+ demonstrated intense inflammation focused at intrahepatic bile ducts, pathology analogous to that found in biliary atresia in humans, and high levels of T3SA+ antigen in bile duct epithelial cells. T3SA+ bound 100-fold more efficiently than T3SA- to human cholangiocarcinoma cells. These observations suggest that the carbohydrate-binding specificity of a virus can dramatically alter disease in the host and highlight the need for epidemiologic studies focusing on infection by sialic acid-binding reovirus strains as a possible contributor to the pathogenesis of neonatal biliary atresia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, Viral / metabolism
  • Bile Ducts / virology
  • Biliary Atresia / etiology*
  • Biliary Atresia / physiopathology
  • Biliary Atresia / virology
  • Cell Line
  • Encephalitis, Viral / etiology
  • Encephalitis, Viral / physiopathology
  • Encephalitis, Viral / virology
  • Genotype
  • Humans
  • Mammalian orthoreovirus 3 / genetics
  • Mammalian orthoreovirus 3 / pathogenicity*
  • Mammalian orthoreovirus 3 / physiology
  • Mice
  • N-Acetylneuraminic Acid / physiology*
  • Phenotype
  • Receptors, Virus / physiology*
  • Reoviridae Infections / complications*
  • Reoviridae Infections / physiopathology
  • Reoviridae Infections / virology
  • Tumor Cells, Cultured
  • Virulence / genetics
  • Virulence / physiology
  • Virus Replication


  • Antigens, Viral
  • Receptors, Virus
  • N-Acetylneuraminic Acid