31:104-111. 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 launched 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 contamination. 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 1-encoding S1 gene segment of the strains chosen for study revealed little conservation in the deduced 1 amino acid sequences among the three serotypes. This contrasts markedly with the observed sequence variability within each serotype, which is usually confined to a small number of amino acids. Mapping of these residues onto the crystal structure of 1 1 recognized regions of conservation and variability, suggesting a likely mode of JAM-A binding via a conserved surface at the base of the 1 head domain name. Mammalian orthoreoviruses (referred to as reoviruses in this article) Nebivolol are nonenveloped viruses with genomes of 10 discrete segments of double-stranded RNA (examined in reference 41). There are at least three serotypes of reoviruses, which can be differentiated by the capacity of antireovirus antisera to neutralize viral infectivity and inhibit hemagglutination (47, 50). Each of the reovirus serotypes is usually represented by a prototype strain, namely, type 1 Lang/53 (T1L/53), type 2 Jones/55 (T2J/55), and type 3 Dearing/55 (T3D/55). Reoviruses appear to infect most mammalian species, but disease Nebivolol is restricted to the very young (examined in reference 63). Reovirus infections of newborn mice have been used as the preferred experimental system for studies of reovirus pathogenesis. Sequence polymorphisms in reovirus attachment protein 1 play an important role in determining sites of reovirus contamination in the infected host (4, 32, 69, 70). The 1 protein is an elongated trimer with a head-and-tail morphology. The N-terminal 1 tail partially inserts into the virion via turrets created by the pentameric 2 protein, while the C-terminal 1 head projects away from Nebivolol the virion surface (1, 25, 26). A crystal structure of the C-terminal half of T3D/55 1 revealed that the head contains three -barrel domains (one from each trimer), each of which is usually constructed from eight antiparallel -strands (16). Sequence analysis and structural modeling have suggested that this N-terminal half of the tail is usually created from an -helical coiled coil (6, 21, 40) and the C-terminal half is usually created from a triple -spiral (16, 56). The overall structural topology of the -spiral and head domains of 1 1 is usually strikingly similar to that of the adenovirus Nes attachment protein, fiber (16, 37, 56). You will find two unique receptor-binding regions in 1. A region in the fibrous tail domain name of type 3 1 binds to -linked sialic acid (2, 14, 15, 18). A distinct region in the type 1 1 tail domain name also binds to cell surface carbohydrates (14), and recent evidence suggests that sialic acid may be involved in the binding of T1L/53 to intestinal cells (30). A second receptor-binding site is located in the head domains of both the type 1 and type 3 1 proteins (3, 39). An expression-cloning approach was used to identify junctional adhesion molecule A (JAM-A) as a receptor for the prototype strains T1L/53 and T3D/55 (3). JAM-A is usually a 35-kDa type I transmembrane protein that is a member of the immunoglobulin superfamily Nebivolol (34, 36). JAM-A contains two immunoglobulin-like domains, a single transmembrane region, and a short cytoplasmic tail. JAM-A.