title: Functional roles of HIV-1 Vpu and CD74: Details and implications of the Vpu-CD74 interaction.
abstract: HIV-1 Vpu has a variety of functions, including CD4 degradation and the downregulation of MHCII. Downregulation of the MHCII occurs through Vpu binding to the cytoplasmic domain of CD74, the chaperone for antigen presentation. The CD74 cytoplasmic domain also plays a vital role in cell signaling through the activation of an NF-κB signal cascade for the maturation, proliferation and survival of B cells as well as by binding the macrophage inhibitory factor. In view of these functions, it follows that the Vpu-CD74 interaction has multiple downstream consequences for the immune system as it not only impairs foreign antigen presentation but may also have an effect on signal transduction cascades. It is thought that Vpu specifically targets intracellular CD74 while other HIV-1 proteins cannot. Therefore, this protein-protein interaction would be a potential drug target in order to reduce viral persistence. We review the functional importance and specific binding site of Vpu and CD74.
authors: Centre for Metal-based Drug Discovery, Mintek, Private Bag X3015, Randburg 2125, South Africa; Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand Medical School, Private Bag 3, WITS, 2050, South Africa. Electronic address: denisel@mintek.co.za.
authors: Denise A
authors: DA
authors: Le Noury
authors: Centre for Metal-based Drug Discovery, Mintek, Private Bag X3015, Randburg 2125, South Africa. Electronic address: salerwem@mintek.co.za.
authors: Salerwe
authors: S
authors: Mosebi
authors: Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand Medical School, Private Bag 3, WITS, 2050, South Africa. Electronic address: Maria.Papathanasopoulos@wits.ac.za.
authors: Maria A
authors: MA
authors: Papathanasopoulos
authors: Centre for Metal-based Drug Discovery, Mintek, Private Bag X3015, Randburg 2125, South Africa. Electronic address: hewerr@ukzn.ac.za.
authors: Raymond
authors: R
authors: Hewer
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001665:Binding Sites; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D015497:HIV-1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000276:immunology; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D054298:Human Immunodeficiency Virus Proteins; D019746:Intramolecular Oxidoreductases; D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; D054334:Viral Regulatory and Accessory Proteins; C045084:invariant chain; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C515598:MIF protein, human
keywords: Antigen presentation; CD74; Cell signaling; Drug target; HIV-1; NF-κB; Vpu