title: HIV-1 Vpu interference with innate cell-mediated immune mechanisms.
abstract: The HIV-1 accessory protein Vpu is emerging as a viral factor with a range of activities devoted to counteracting host innate immunity. Here, we review recent findings concerning the role of Vpu in hampering activation of cellular immune responses mediated by CD1d-restricted invariant natural killer T (iNKT) cells and natural killer (NK) cells. The two key findings are that Vpu interferes with CD1d expression and antigen presentation, and also with expression of the NK cell activation ligand NK-T and B cell antigen (NTB-A). Both these activities are mechanistically distinct from CD4 and Tetherin (BST-2) down-modulation. We summarize the mechanistic insights gained into Vpu interference with CD1d and NTB-A, as well as important challenges going forward, and discuss these mechanisms in the context of the role that iNKT and NK cells play in HIV-1 immunity and immunopathogenesis.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. johan.sandberg@ki.se
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.forename: Sofia K
authors.initials: SK
authors.lastname: Andersson
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Bächle
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Markus
authors.initials: M
authors.lastname: Moll
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D055611:Natural Killer T-Cells / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D054334:Viral Regulatory and Accessory Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D055610:Antigens, CD1d; D054298:Human Immunodeficiency Virus Proteins; D011956:Receptors, Cell Surface; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D054334:Viral Regulatory and Accessory Proteins; C000604060:SLAMF6 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins