title: Involvement of a C-terminal motif in the interference of primate lentiviral Vpu proteins with CD1d-mediated antigen presentation.
abstract: The HIV-1 accessory protein Vpu is emerging as a critical factor for viral evasion from innate immunity. We have previously shown that the Vpu proteins of two HIV-1 group M subtype B strains (NL4-3 and BaL) down-regulate CD1d from the surface of infected dendritic cells (DCs) and inhibit their crosstalk with the innate invariant natural killer T (iNKT) cells. In the present study, we have investigated the ability of a comprehensive set of primate lentiviral Vpu proteins to interfere with CD1d-mediated immunity. We found that CD1d down-regulation is a conserved function of Vpu proteins from HIV-1 groups M, O and P as well as their direct precursors SIVcpzPtt and SIVgor. At the group M subtype level, subtype C Vpu proteins were significantly weaker CD1d antagonists than subtype B Vpu proteins. Functional characterization of different mutants and chimeras derived from active subtype B and inactive subtype C Vpu proteins revealed that residues in the cytoplasmic domain are important for CD1d down-regulation. Specifically, we identified a C-terminal APW motif characteristic for group M subtype B Vpu proteins necessary for interference with CD1d surface expression. These findings support the notion that Vpu plays an important role in lentiviral evasion from innate immunity.
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
authors: Susanna M
authors: SM
authors: Bächle
authors: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors: Daniel
authors: D
authors: Sauter
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
authors: Sabrina
authors: S
authors: Sibitz
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
authors: Johan K
authors: JK
authors: Sandberg
authors: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors: Frank
authors: F
authors: Kirchhoff
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
authors: Markus
authors: M
authors: Moll
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D055610:Antigens, CD1d / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D015536:Down-Regulation; D015870:Gene Expression; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017958:Lentiviruses, Primate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D056510:Position-Specific Scoring Matrices; D054730:Protein Interaction Domains and Motifs; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D055610:Antigens, CD1d; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins