Receptors expressed around the web host cell surface area adhere viruses to focus on cells and serve seeing that determinants of viral tropism. glycans recommending that glycan-binding capability plays a part in these distinctions in pathogenesis. Using structure-guided mutagenesis we built a mutant T1 reovirus not capable of binding the T1 reovirus-specific glycan receptor GM2. The mutant pathogen induced substantially much less hydrocephalus than wild-type pathogen an Angiotensin 1/2 (1-9) impact phenocopied by wild-type pathogen infections of GM2-lacking mice. Compared to wild-type pathogen produces of mutant pathogen were reduced in cultured ependymal cells the cell type that lines the mind ventricles. These results claim that GM2 engagement goals reovirus to ependymal Angiotensin 1/2 (1-9) cells in mice and illuminate the function of glycan engagement in reovirus serotype-dependent disease. IMPORTANCE Receptor usage highly affects viral disease frequently dictating web host range and focus on cell selection. Different reovirus serotypes bind to different glycans but a precise function for these molecules in pathogenesis is usually unknown. We used type 1 (T1) reovirus deficient in binding the GM2 glycan and mice lacking GM2 to pinpoint a role for glycan engagement in hydrocephalus caused by T1 reovirus. This work indicates that engagement of a specific glycan can lead to infection of specific cells in the host and consequent disease at that site. Since reovirus is being developed as a vaccine vector and oncolytic agent understanding reovirus-glycan interactions Angiotensin 1/2 (1-9) may allow manipulation of reovirus glycan-binding properties for therapeutic applications. INTRODUCTION Viruses are capable of binding a variety of cell surface receptors to initiate the process of contamination. Many viruses use glycans to facilitate attachment and access (1 -6). Some viruses such as influenza computer virus appear to participate glycans as Angiotensin 1/2 (1-9) a main receptor (5) while others such as herpes simplex virus (7) and Rabbit Polyclonal to Merlin (phospho-Ser10). reovirus (1 8 participate glycans as an initial adhesive event prior to binding a proteinaceous attachment receptor in a process known as adhesion strengthening. Virus-glycan interactions govern cell susceptibility yet the contribution of individual glycans to viral pathogenesis is not understood for most glycan-binding viruses. Mammalian reoviruses display serotype-dependent pathology in the murine central nervous system (CNS). Serotype 1 (T1) reovirus spreads via Angiotensin 1/2 (1-9) hematogenous routes (9 -11) and infects ependymal cells (12 13 resulting in hydrocephalus (13 14 Conversely serotype 3 (T3) reovirus disseminates via neural and hematogenous routes (15 -17) infects CNS neurons and causes lethal encephalitis (9 18 -20). The basis for these serotype-specific differences in neuropathogenesis is not known. However studies using reassortant strains (i.e. strains made up of mixtures of gene segments derived from two parental strains) demonstrate that this viral S1 gene which encodes attachment protein σ1 dictates serotype-dependent differences in CNS pathology (9 11 17 18 These findings suggest that differences in CNS disease likely are attributable to differential engagement of cell surface receptors. While T1 and T3 reovirus participate the Angiotensin 1/2 (1-9) same known protein receptors junctional adhesion molecule A (JAM-A) (8) and Nogo receptor 1 (NgR1) (21) the different reovirus serotypes interact with unique glycans. We previously exhibited that T1 reovirus binds the GM2 glycan which is a branched oligosaccharide composed of a glucose and galactose backbone with terminal α2 3 sialic acid (Neu5Ac) and β1 4 neuraminidase which removes cell surface sialic acid or phosphate-buffered saline (PBS) as a control prior to incubation with strain T1L as well as the S370P/Q371E mutant. T1L-mediated hemagglutination was impaired pursuing neuraminidase treatment whereas S370P/Q371E had not been (Fig.?1B) indicating that the rest of the hemagglutination capacity from the S370P/Q371E mutant isn’t due to sialylated glycan engagement. Needlessly to say hemagglutination activity of prototype T3 stress type 3 Dearing (T3D) was abolished by neuraminidase treatment of erythrocytes (26). Incubation of wild-type and mutant T1 reovirus strains with T1 σ1-particular MAb 5C6 avoided hemagglutination but acquired no influence on hemagglutination by stress T3D (Fig.?1B). These results claim that T1L however not the.