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

Barton ES, Youree BE, Ebert DH, Forrest JC, Connolly JL, Valyi-Nagy T, Washington K, Wetzel JD, Dermody TS
J Clin Invest. 2003 111 (12): 1823-33

PMID: 12813018 · PMCID: PMC161418 · 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.

MeSH Terms (18)

Animals Animals, Newborn Antigens, Viral Bile Ducts Biliary Atresia Cell Line Encephalitis, Viral Genotype Humans Mammalian orthoreovirus 3 Mice N-Acetylneuraminic Acid Phenotype Receptors, Virus Reoviridae Infections Tumor Cells, Cultured Virulence Virus Replication

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