title: From touchdown to transcription: the reovirus cell entry pathway.
abstract: Mammalian orthoreoviruses (reoviruses) are prototype members of the Reoviridae family of nonenveloped viruses. Reoviruses contain ten double-stranded RNA gene segments enclosed in two concentric protein shells, outer capsid and core. These viruses serve as a versatile experimental system for studies of virus cell entry, innate immunity, and organ-specific disease. Reoviruses engage cells by binding to cell-surface carbohydrates and the immunoglobulin superfamily member, junctional adhesion molecule-A (JAM-A). JAM-A is a homodimer formed by extensive contacts between its N-terminal immunoglobulin-like domains. Reovirus attachment protein σ1 disrupts the JAM-A dimer, engaging a single JAM-A molecule by virtually the same interface used for JAM-A homodimerization. Following attachment to JAM-A and carbohydrate, reovirus internalization is promoted by β1 integrins, most likely via clathrin-dependent endocytosis. In the endocytic compartment, reovirus outer-capsid protein σ3 is removed by cathepsin proteases, which exposes the viral membrane-penetration protein, μ1. Proteolytic processing and conformational rearrangements of μ1 mediate endosomal membrane rupture and delivery of transcriptionally active reovirus core particles into the host cell cytoplasm. These events also allow the φ cleavage fragment of μ1 to escape into the cytoplasm where it activates NF-κB and elicits apoptosis. This review will focus on mechanisms of reovirus cell entry and activation of innate immune response signaling pathways.
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN, 47405, USA.
authors.forename: Pranav
authors.initials: P
authors.lastname: Danthi
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Guglielmi
authors.forename: Eva
authors.initials: E
authors.lastname: Kirchner
authors.forename: Bernardo
authors.initials: B
authors.lastname: Mainou
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D004705:Endocytosis; D006801:Humans; D007113:Immunity, Innate; D007136:Immunoglobulins / Q000502:physiology; D019012:Integrin beta1 / Q000502:physiology; D011956:Receptors, Cell Surface; D012087:Reoviridae / Q000502:physiology* / Q000648:ultrastructure; D014771:Virion / Q000648:ultrastructure; D019065:Virus Assembly; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D007136:Immunoglobulins; D019012:Integrin beta1; D011956:Receptors, Cell Surface
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