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

• Published in: The Journal of clinical investigation Vol. 111; no. 12; pp. 1823 - 1833
• Main Authors: Barton, E S, Youree, B E, Ebert, D H, rest, J C, Connolly, J L, Valyi-Nagy, T, Washington, K, Wetzel, J D, Dermody, T S
• Format: Journal Article
• Language: English
• Published: American Society for Clinical Investigation 01-06-2003
• Subjects: Reovirus
• ISSN: 0021-9738
• DOI: 10.1172/JCI200316303

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.