title: Utilization of sialic acid as a coreceptor is required for reovirus-induced biliary disease.
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.
authors.affiliation: Department of Microbiology and Immunology and Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Barton
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Youree
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Ebert
authors.forename: J Craig
authors.initials: JC
authors.lastname: Forrest
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Connolly
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.forename: Kay
authors.initials: K
authors.lastname: Washington
authors.forename: J Denise
authors.initials: JD
authors.lastname: Wetzel
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000378:metabolism; D001652:Bile Ducts / Q000821:virology; D001656:Biliary Atresia / Q000209:etiology* / Q000503:physiopathology / Q000821:virology; D002460:Cell Line; D018792:Encephalitis, Viral / Q000209:etiology / Q000503:physiopathology / Q000821:virology; D005838:Genotype; D006801:Humans; D012089:Mammalian orthoreovirus 3 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000502:physiology*; D010641:Phenotype; D011991:Receptors, Virus / Q000502:physiology*; D012088:Reoviridae Infections / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D014407:Tumor Cells, Cultured; D014774:Virulence / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid