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

Erik S. Barton, Bryan E. Youree, Daniel Ebert, J. Craig Forrest, Jodi L. Connolly, Tibor Valyi-Nagy, Kay Washington, J. Denise Wetzel, Terence S. Dermody

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1823-1833
Number of pages11
JournalJournal of Clinical Investigation
Volume111
Issue number12
DOIs
Publication statusPublished - Jun 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Barton, E. S., Youree, B. E., Ebert, D., Forrest, J. C., Connolly, J. L., Valyi-Nagy, T., ... Dermody, T. S. (2003). Utilization of sialic acid as a coreceptor is required for reovirus-induced biliary disease. Journal of Clinical Investigation, 111(12), 1823-1833. https://doi.org/10.1172/JCI200316303