title: In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans.
abstract: Human CD317 is an intrinsic immunity factor that restricts the release of enveloped viruses, including the major pathogens HIV and Lassa virus, from infected cells in culture. Its importance for infection control in humans is unclear, due in part to its incompletely defined in vivo expression pattern. CD317 also has been proposed as a selective target for immunotherapy of multiple myeloma. To provide a framework for studies of the biological functions, regulation, and therapeutic potential of CD317, we performed microarray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type-dependent coexpression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317's widespread expression calls into question its suitability as a target for immunotherapy.
authors.affiliation: Department of Infectious Diseases, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Elina
authors.initials: E
authors.lastname: Erikson
authors.forename: Tarek
authors.initials: T
authors.lastname: Adam
authors.forename: Sarah
authors.initials: S
authors.lastname: Schmidt
authors.forename: Judith
authors.initials: J
authors.lastname: Lehmann-Koch
authors.forename: Benjamin
authors.initials: B
authors.lastname: Over
authors.forename: Christine
authors.initials: C
authors.lastname: Goffinet
authors.forename: Christoph
authors.initials: C
authors.lastname: Harter
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bekeredjian-Ding
authors.forename: Serkan
authors.initials: S
authors.lastname: Sertel
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Keppler
mesh_terms: D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis; D000998:Antiviral Agents / Q000032:analysis; D058851:GPI-Linked Proteins / Q000032:analysis / Q000276:immunology; D006801:Humans; D007109:Immunity; D007372:Interferons / Q000032:analysis; D040081:Protein Array Analysis; D013045:Species Specificity; D046888:Tissue Array Analysis; D014018:Tissue Distribution; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000998:Antiviral Agents; D058851:GPI-Linked Proteins; D007372:Interferons; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2