Emerging role of the host restriction factor tetherin in viral immune sensing.
Tetherin (BST-2, CD317) is an interferon-inducible cellular factor that inhibits the release of diverse enveloped viruses by tethering them to the cell surface. Its importance in antiviral immunity is underscored by the observation that various viruses have evolved antagonists against this restriction factor. Accumulating evidence suggests that this is not only due to its ability to inhibit virus release but that tetherin also acts as an innate immune sensor of viral infections that activates NF-κB to induce an inflammatory response. Furthermore, tetherin modulates immune activation through interactions with the immunoglobulin-like transcript 7 (ILT7, LILRA4). This surface receptor is specifically expressed on plasmacytoid dendritic cells, which are the main producers of type I interferons in response to viral infections. Here, we summarize some of our current knowledge about the role of tetherin as a viral immune sensor and discuss how the accessory HIV-1 (human immunodeficiency virus type 1) Vpu protein counteracts this effect.
Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Dominik
D
Hotter
Daniel
D
Sauter
Frank
F
Kirchhoff
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D018448:Models, Immunological; D008969:Molecular Sequence Data; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D052002:NF-kappa B p50 Subunit; D011971:Receptors, Immunologic; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C488262:LILRA4 protein, human; C489548:NFKB1 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
DC; GPI; HIV-1; IFN; ILT7; IRF; PRR; SAMHD1; SIV; TAB; TAK1; TAK1-binding protein; TLR; TNF receptor-associated factor; TRAF; Toll-like receptor; Vpu; dendritic cell; glycosyl-phosphatidylinositol; human immunodeficiency virus type 1; immune signaling; immunoglobulin-like transcript 7; interferon; interferon regulatory factor; pDC; pattern-recognition receptor; plasmacytoid dendritic cell; simian immunodeficiency virus; sterile alpha motif and histidine/aspartic acid domain-containing protein 1; tetherin; transforming growth factor-β-activated kinase-1