title: The Nogo receptor NgR1 mediates infection by mammalian reovirus.
abstract: Neurotropic viruses, including mammalian reovirus, must disseminate from an initial site of replication to the central nervous system (CNS), often binding multiple receptors to facilitate systemic spread. Reovirus engages junctional adhesion molecule A (JAM-A) to disseminate hematogenously. However, JAM-A is dispensable for reovirus replication in the CNS. We demonstrate that reovirus binds Nogo receptor NgR1, a leucine-rich repeat protein expressed in the CNS, to infect neurons. Expression of NgR1 confers reovirus binding and infection of nonsusceptible cells. Incubating reovirus virions with soluble NgR1 neutralizes infectivity. Blocking NgR1 on transfected cells or primary cortical neurons abrogates reovirus infection. Concordantly, reovirus infection is ablated in primary cortical neurons derived from NgR1 null mice. Reovirus virions bind to soluble JAM-A and NgR1, while infectious disassembly intermediates (ISVPs) bind only to JAM-A. These results suggest that reovirus uses different capsid components to bind distinct cell-surface molecules, engaging independent receptors to facilitate spread and tropism.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Konopka-Anstadt
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Mainou
authors.affiliation: Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Danica M
authors.initials: DM
authors.lastname: Sutherland
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Departments of Neurobiology and Neurology, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Departments of Neurobiology and Neurology, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: terry.dermody@vanderbilt.edu.
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000821:virology; D036022:Capsid Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D003412:Cricetulus; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008817:Mice, Mutant Strains; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009439:Neuraminidase / Q000737:chemistry; D009474:Neurons / Q000821:virology; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012087:Reoviridae / Q000378:metabolism* / Q000472:pathogenicity; D012088:Reoviridae Infections / Q000378:metabolism / Q000821:virology; D014771:Virion / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse; D009439:Neuraminidase