title: GRP78, a coreceptor for coxsackievirus A9, interacts with major histocompatibility complex class I molecules which mediate virus internalization.
abstract: It is becoming apparent that over the years cell infection by virus seems to have evolved into a multistep process in which many viruses employ distinct cell surface molecules for their attachment and cell entry. In this study the attachment and entry pathway of coxsackievirus A9 (CAV-9), a member of the Picornaviridae family, was investigated. It has been known that, although integrin alpha(v)beta3 is utilized as a receptor, its presence alone is insufficient for CAV-9 infection and that CAV-9 also requires a 70-kDa major histocompatibility complex class I (MHC-I)-associated protein (MAP-70) as a coreceptor molecule. We document by protein isolation and peptide sequencing that the 70-kDa protein is GRP78, a member of the heat shock protein 70 family of stress proteins. Furthermore we show by using fluorescence resonance energy transfer (FRET) that GRP78 is also expressed on the cell surface and associates with MHC-I molecules. In addition CAV-9 infection of permissive cells requires GRP78 and also MHC-I molecules, which are essential for virus internalization. The identification of GRP78 as a coreceptor for CAV-9 and the revelation of GRP78 and MHC-I associations have provided new insights into the life cycle of CAV-9, which utilizes integrin alpha(v)beta3 and GRP78 as receptor molecules whereas MHC-I molecules serve as the internalization pathway of this virus to mammalian cells.
authors.affiliation: School of Biological Sciences, University of Portsmouth, Portsmouth PO1 2DY, United Kingdom.
authors.forename: Kathy
authors.initials: K
authors.lastname: Triantafilou
authors.forename: Didier
authors.initials: D
authors.lastname: Fradelizi
authors.forename: Keith
authors.initials: K
authors.lastname: Wilson
authors.forename: Martha
authors.initials: M
authors.lastname: Triantafilou
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis; D000091342:Endoplasmic Reticulum Chaperone BiP; D004735:Energy Transfer; D004770:Enterovirus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005434:Flow Cytometry; D005453:Fluorescence; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010948:Viral Plaque Assay; D014779:Virus Replication
chemical_list: D000906:Antibodies; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D018832:Molecular Chaperones; D011991:Receptors, Virus