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

ES Barton, BE Youree, DH Ebert… - The Journal of …, 2003 - Am Soc Clin Investig
ES Barton, BE Youree, DH Ebert, JC Forrest, JL Connolly, T Valyi-Nagy, K Washington…
The Journal of clinical investigation, 2003Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation