title: Junctional adhesion molecule a serves as a receptor for prototype and field-isolate strains of mammalian reovirus.
abstract: Reovirus infections are initiated by the binding of viral attachment protein sigma1 to receptors on the surface of host cells. The sigma1 protein is an elongated fiber comprised of an N-terminal tail that inserts into the virion and a C-terminal head that extends from the virion surface. The prototype reovirus strains type 1 Lang/53 (T1L/53) and type 3 Dearing/55 (T3D/55) use junctional adhesion molecule A (JAM-A) as a receptor. The C-terminal half of the T3D/55 sigma1 protein interacts directly with JAM-A, but the determinants of receptor-binding specificity have not been identified. In this study, we investigated whether JAM-A also mediates the attachment of the prototype reovirus strain type 2 Jones/55 (T2J/55) and a panel of field-isolate strains representing each of the three serotypes. Antibodies specific for JAM-A were capable of inhibiting infections of HeLa cells by T1L/53, T2J/55, and T3D/55, demonstrating that strains of all three serotypes use JAM-A as a receptor. To corroborate these findings, we introduced JAM-A or the structurally related JAM family members JAM-B and JAM-C into Chinese hamster ovary cells, which are poorly permissive for reovirus infection. Both prototype and field-isolate reovirus strains were capable of infecting cells transfected with JAM-A but not those transfected with JAM-B or JAM-C. A sequence analysis of the sigma1-encoding S1 gene segment of the strains chosen for study revealed little conservation in the deduced sigma1 amino acid sequences among the three serotypes. This contrasts markedly with the observed sequence variability within each serotype, which is confined to a small number of amino acids. Mapping of these residues onto the crystal structure of sigma1 identified regions of conservation and variability, suggesting a likely mode of JAM-A binding via a conserved surface at the base of the sigma1 head domain.
authors.affiliation: Department of Microbiology and Immunology, Elizabeth B. Lamb Center for Pediatric Research, D7235 MCN, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Campbell
authors.forename: Pierre
authors.initials: P
authors.lastname: Schelling
authors.forename: J Denise
authors.initials: JD
authors.lastname: Wetzel
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Johnson
authors.forename: J Craig
authors.initials: JC
authors.lastname: Forrest
authors.forename: Greame A R
authors.initials: GA
authors.lastname: Wilson
authors.forename: Michel
authors.initials: M
authors.lastname: Aurrand-Lions
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000502:physiology*; D006224:Cricetinae; D017931:DNA Primers; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D062726:Junctional Adhesion Molecules; D007739:L Cells; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000502:physiology*; D012087:Reoviridae / Q000145:classification / Q000302:isolation & purification*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019108:Tight Junctions / Q000821:virology
chemical_list: D015815:Cell Adhesion Molecules; D017931:DNA Primers; D062726:Junctional Adhesion Molecules; D011991:Receptors, Virus