nef

Summary

Gene Symbol: nef
Description: p27
Alias: Nef
Species: human immunodeficiency virus 1

Top Publications

  1. ncbi Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4
    K Saksela
    Rockefeller University, New York, NY 10021
    EMBO J 14:484-91. 1995
  2. ncbi Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein
    O Schwartz
    Laboratoire Rétrovirus et Transfert Génétique, Unité de Recherche Associée CNRS 1157, Paris, France
    Nat Med 2:338-42. 1996
  3. ncbi HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction
    Ronald P Trible
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:27029-38. 2006
  4. ncbi Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators
    A Simmons
    MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
    Immunity 14:763-77. 2001
  5. ncbi The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling
    S Arold
    Centre de Biochimie Structurale, UMR C9955 CNRS, U414 INSERM, Universite Montpellier I, Faculte de Pharmacie, France
    Structure 5:1361-72. 1997
  6. ncbi Protein protein interaction inhibition (2P2I) combining high throughput and virtual screening: Application to the HIV-1 Nef protein
    Stephane Betzi
    Bioénergétique et Ingénierie des Protéines Laboratory, Centre National de la Recherche Scientifique Institut de Biologie Structurale et Microbiologie, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France
    Proc Natl Acad Sci U S A 104:19256-61. 2007
  7. ncbi HIV-1 Nef upregulates CCL2/MCP-1 expression in astrocytes in a myristoylation- and calmodulin-dependent manner
    Michael H Lehmann
    Institute of Molecular Virology, GSF National Research Center for Environment and Health, Ingolstadter Landstr 1, 85764 Neuherberg, Germany
    J Cell Sci 119:4520-30. 2006
  8. ncbi HIV-Nef enhances interleukin-2 production and phosphatidylinositol 3-kinase activity in a human T cell line
    S D Schibeci
    Department of Clinical Immunology, Westmead Hospital, NSW, Australia
    AIDS 14:1701-7. 2000
  9. ncbi Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1
    Michael Schindler
    Department of Virology, University of Ulm, 89081 Ulm, Germany
    Cell 125:1055-67. 2006
  10. ncbi Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain
    C Aiken
    Infectious Disease Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037 1099
    Cell 76:853-64. 1994

Research Grants

  1. HIV-1 Vpu and BST-2/CD317
    John Guatelli; Fiscal Year: 2010
  2. The MHC-I, HIV-1 Nef, AP-1 Complex
    John Guatelli; Fiscal Year: 2007
  3. Role of specific Nef functions in AIDS pathogenesis
    Frank Kirchhoff; Fiscal Year: 2007
  4. HIV 1 NEF AND VIRAL INFECTIVITY
    John Guatelli; Fiscal Year: 2007
  5. PROTEIN PROFILING OF ORAL MUCOSA OF HIV TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2007
  6. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2007
  7. Factors/HIV-1 Nef's Ability to Direct Immune Evasion
    Martha Lewis; Fiscal Year: 2007
  8. Role of HIPK2 in Kidney Tubulointerstitial Injury
    AVI MA apos AYAN; Fiscal Year: 2010
  9. HIV-1 Vpu and BST-2/CD317
    John Guatelli; Fiscal Year: 2011
  10. HIV 1 NEF AND VIRAL INFECTIVITY
    John Guatelli; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications105 found, 100 shown here

  1. ncbi Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4
    K Saksela
    Rockefeller University, New York, NY 10021
    EMBO J 14:484-91. 1995
    Human immunodeficiency virus (HIV) and simian immunodeficiency virus Nef proteins contain a conserved motif with the minimal consensus (PxxP) site for Src homology region 3 (SH3)-mediated protein-protein interactions...
  2. ncbi Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein
    O Schwartz
    Laboratoire Rétrovirus et Transfert Génétique, Unité de Recherche Associée CNRS 1157, Paris, France
    Nat Med 2:338-42. 1996
    ..We have observed that this phenomenon depends on the expression of Nef. nef is an early gene of primate lentiviruses, which is necessary for maintaining high virus loads and inducing ..
  3. ncbi HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction
    Ronald P Trible
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:27029-38. 2006
    b>Nef is an HIV-1 virulence factor that promotes viral pathogenicity by altering host cell signaling pathways. Nef binds several members of the Src kinase family, and these interactions have been implicated in the pathogenesis of HIV/AIDS...
  4. ncbi Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators
    A Simmons
    MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
    Immunity 14:763-77. 2001
    Gene expression profiling was used to explore the role of Nef in HIV. Nef induces a transcriptional program in T cells that is 97% identical to that of anti-CD3 T cell activation. This program is inhibited in the presence of cyclosporin...
  5. ncbi The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling
    S Arold
    Centre de Biochimie Structurale, UMR C9955 CNRS, U414 INSERM, Universite Montpellier I, Faculte de Pharmacie, France
    Structure 5:1361-72. 1997
    Human immunodeficiency virus (HIV) Nef protein accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation...
  6. ncbi Protein protein interaction inhibition (2P2I) combining high throughput and virtual screening: Application to the HIV-1 Nef protein
    Stephane Betzi
    Bioénergétique et Ingénierie des Protéines Laboratory, Centre National de la Recherche Scientifique Institut de Biologie Structurale et Microbiologie, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France
    Proc Natl Acad Sci U S A 104:19256-61. 2007
    ..used as starting point in a structure-based research program that targets an SH3 binding surface of the HIV type I Nef protein...
  7. ncbi HIV-1 Nef upregulates CCL2/MCP-1 expression in astrocytes in a myristoylation- and calmodulin-dependent manner
    Michael H Lehmann
    Institute of Molecular Virology, GSF National Research Center for Environment and Health, Ingolstadter Landstr 1, 85764 Neuherberg, Germany
    J Cell Sci 119:4520-30. 2006
    ..The accessory HIV-1 negative factor (Nef) protein, which modulates several signaling pathways, is constitutively present in persistently infected astroctyes...
  8. ncbi HIV-Nef enhances interleukin-2 production and phosphatidylinositol 3-kinase activity in a human T cell line
    S D Schibeci
    Department of Clinical Immunology, Westmead Hospital, NSW, Australia
    AIDS 14:1701-7. 2000
    The Nef protein has a major influence on disease pathogenesis in HIV-infected individuals. The objective of the present study was to examine the effects of Nef on T lymphocyte activation and associated signalling events.
  9. ncbi Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1
    Michael Schindler
    Department of Virology, University of Ulm, 89081 Ulm, Germany
    Cell 125:1055-67. 2006
    ..The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T ..
  10. ncbi Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain
    C Aiken
    Infectious Disease Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037 1099
    Cell 76:853-64. 1994
    ..The HIV early protein Nef causes a loss of CD4 from cell surfaces through a previously undefined posttranscriptional mechanism...
  11. ncbi Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions
    O T Fackler
    Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco 94143 0703, USA
    Mol Cell 3:729-39. 1999
    b>Nef of primate lentiviruses is critical for high levels of viremia and the progression to AIDS. Nef associates with and activates a serine/threonine kinase (Nef-associated kinase [NAK]) via the small GTPases Rac1 and Cdc42...
  12. ncbi Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue
    Michael Schindler
    Institute of Virology, Universitatsklinikum, 89081 Ulm, Germany
    J Virol 81:13005-14. 2007
    Interaction of the human immunodeficiency virus type 1 (HIV-1) Nef protein with p21-activated kinase 2 (PAK2) has been proposed to play a role in T-cell activation, viral replication, apoptosis, and progression to AIDS...
  13. ncbi A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4
    M Greenberg
    Cold Spring Harbor Laboratory, New York 11724, USA
    Curr Biol 8:1239-42. 1998
    b>Nef, a approximately 200 residue multifunctional regulatory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), interacts with components of host cell signal transduction and clathrin-dependent protein ..
  14. ncbi Heat shock protein 40 is necessary for human immunodeficiency virus-1 Nef-mediated enhancement of viral gene expression and replication
    Manish Kumar
    National Centre for Cell Science, Ganeshkhind, Pune 411007, India
    J Biol Chem 280:40041-50. 2005
    The human immunodeficiency virus-1 (HIV-1) Nef protein, originally identified as a negative factor, has now emerged as one of the most important viral proteins necessary for viral pathogenesis and disease progression...
  15. ncbi The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells
    G B Cohen
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Immunity 10:661-71. 1999
    ..These results suggest that subpopulations of CTL and NK cells may be uniquely suited for combating HIV...
  16. ncbi Activation of PAK by HIV and SIV Nef: importance for AIDS in rhesus macaques
    E T Sawai
    Department of Medical Pathology, University of California, Davis 95616, USA
    Curr Biol 6:1519-27. 1996
    ..types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), encode a conserved accessory gene product, Nef. In vivo, Nef is important for the maintenance of high virus loads and progression to AIDS in SIV-infected adult ..
  17. ncbi A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells
    O T Fackler
    Institute for Hygiene, Department of Virology, University of Heidelberg, D 69120, Heidelberg, Germany
    Curr Biol 11:1294-9. 2001
    In the infected host, the Nef protein of HIV/SIV is required for high viral loads and thus disease progression...
  18. ncbi Proline 78 is crucial for human immunodeficiency virus type 1 Nef to down-regulate class I human leukocyte antigen
    Takeshi Yamada
    Division of Infectious Diseases, Advanced Clinical Research Center, The University of Tokyo, Japan
    J Virol 77:1589-94. 2003
    Human immunodeficiency virus type 1 Nef down-regulates human leukocyte antigen class I (HLA-I) in T lymphocytes, and the down-regulation involves the Nef proline-rich domain (PRD) containing four prolines at positions 69, 72, 75, and 78...
  19. ncbi Activation of NFAT-dependent gene expression by Nef: conservation among divergent Nef alleles, dependence on SH3 binding and membrane association, and cooperation with protein kinase C-theta
    A Manninen
    Institute of Medical Technology, University of Tampere, FIN 33014 Tampere, Finland
    J Virol 75:3034-7. 2001
    Here we show that the potential to regulate NFAT is a conserved property of different Nef alleles and that Nef residues involved in membrane targeting and SH3 binding are critical for this function...
  20. ncbi Subunit H of the V-ATPase involved in endocytosis shows homology to beta-adaptins
    Matthias Geyer
    Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, California 94143 0703, USA
    Mol Biol Cell 13:2045-56. 2002
    ..For beta-adaptins, this fragment binds to cytoplasmic di-leucine-based sorting motifs such as in HIV-1 Nef that mediate endocytic trafficking...
  21. ncbi HIV type 1 nef gene inhibits tumor necrosis factor alpha-induced apoptosis and promotes cell proliferation through the action of MAPK and JNK in human glial cells
    G A Robichaud
    Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Quebec, Canada G1V 4G2
    AIDS Res Hum Retroviruses 16:1959-65. 2000
    ..Whereas the HIV-1 nef gene is overexpressed during restricted HIV-1 infection of human astrocytes, our previous results have demonstrated ..
  22. ncbi Stable expression of HIV-1 Nef induces changes in growth properties and activation state of human astrocytes
    B Kohleisen
    GSF National Research Center for Environment and Health, Institute of Molecular Virology, Neuherberg, Germany
    AIDS 13:2331-41. 1999
    b>Nef was shown to be the predominant viral protein expressed in HIV-1-infected astrocytes in vivo and in vitro suggesting a distinct role of Nef in this cell type...
  23. ncbi Regulation of human immunodeficiency virus Nef protein by phosphorylation
    J C Bandres
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri
    Virology 201:157-61. 1994
    Human immunodeficiency virus isolates express a Nef protein with either an alanine or a threonine at amino acid residue 15. The threonine residue is a site for phosphorylation by protein kinase C...
  24. ncbi Molecular analysis of the cytoplasmic domain of CD4: overlapping but noncompetitive requirement for lck association and down-regulation by Nef
    S Gratton
    Laboratory of Immunology, Clinical Research Institute of Montreal, Quebec, Canada
    J Immunol 157:3305-11. 1996
    Expression of the HIV Nef protein results in the down-regulation of cell surface expression of CD4, with a di-leucine motif in the cytoplasmic domain of CD4 being required for this effect...
  25. ncbi Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family
    M F Nunn
    Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892, USA
    J Virol 70:6157-61. 1996
    Although human immunodeficiency virus (HIV) Nef is essential for the induction of AIDS, its biochemical function has remained an enigma...
  26. ncbi Separable functions of Nef disrupt two aspects of T cell receptor machinery: CD4 expression and CD3 signaling
    A J Iafrate
    Department in Molecular Genetics and Microbiology, SUNY at Stony Brook, NY 11794, USA
    EMBO J 16:673-84. 1997
    The Nef protein alters T cell receptor (TCR) signaling in T cells and is critical for the pathogenesis of AIDS. We used a transient expression assay in a human CD4+ T cell line to analyze the interaction of Nef with the TCR machinery...
  27. ncbi Human immunodeficiency virus type 1 Nef induces programmed death 1 expression through a p38 mitogen-activated protein kinase-dependent mechanism
    Karuppiah Muthumani
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Virol 82:11536-44. 2008
    ..Here, we provide evidence that the HIV type 1 (HIV-1) accessory protein Nef can transcriptionally induce the expression of PD-1 during infection in vitro...
  28. ncbi Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation
    H Akari
    Department of Virology, The University of Tokushima School of Medicine, Tokushima, Tokushima 770 8503, Japan
    J Virol 74:2907-12. 2000
    The N-terminal alpha-helix domain of the human immunodeficiency virus type 1 (HIV-1) Nef protein plays important roles in enhancement of viral infectivity, virion incorporation of Nef, and the down-regulation of major histocompatibility ..
  29. ncbi Nef induces multiple genes involved in cholesterol synthesis and uptake in human immunodeficiency virus type 1-infected T cells
    Angélique B van 't Wout
    Department of Microbiology, University of Washington School of Medicine, Seattle, 98195, USA
    J Virol 79:10053-8. 2005
    ..demonstrate that changes in cholesterol biosynthesis and uptake are only observed in the presence of functional Nef, suggesting that increased cholesterol synthesis may contribute to Nef-mediated enhancement of virion infectivity ..
  30. ncbi HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages
    S Swingler
    University of Massachusetts Medical Center, Program in Molecular Medicine, 373 Plantation Street, Worcester, Massachusetts 01605, USA
    Nat Med 5:997-103. 1999
    ..Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, by HIV-1-infected ..
  31. ncbi HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell
    R Geleziunas
    Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, California 94141 9100, USA
    Nature 410:834-8. 2001
    ..Increased killing of such bystander cells is mediated in part through Nef induction of Fas ligand (FasL) expression on the surface of the virally infected T cells...
  32. ncbi A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2
    O Wolf Lindwasser
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Building 18T, Room 101, National Institutes of Health, Bethesda, MD 20892, USA
    J Virol 82:1166-74. 2008
    A key function of the Nef protein of immunodeficiency viruses is the downregulation of the T-cell and macrophage coreceptor, CD4, from the surfaces of infected cells...
  33. ncbi HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway
    Anastassia D Blagoveshchenskaya
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Cell 111:853-66. 2002
    The HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the trans-Golgi network (TGN) enables HIV-1 to escape immune surveillance. However, the cellular pathway used by Nef to downregulate MHC-I is unknown...
  34. ncbi Primary human immunodeficiency virus type 1 nef alleles show major differences in pathogenicity in transgenic mice
    Elena Priceputu
    Laboratory of Molecular Biology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
    J Virol 81:4677-93. 2007
    We previously reported that the human immunodeficiency virus type 1 NL4-3 Nef is necessary and sufficient to induce a severe AIDS-like disease in transgenic (Tg) mice when the protein is expressed under the regulatory sequences of the ..
  35. ncbi Human Immunodeficiency virus type 1 Nef potently induces apoptosis in primary human brain microvascular endothelial cells via the activation of caspases
    Edward A Acheampong
    Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
    J Virol 79:4257-69. 2005
    The lentiviral protein Nef plays a major role in the pathogenesis of human immunodeficiency virus type I (HIV-1) infection...
  36. ncbi Oligomerization is required for HIV-1 Nef-induced activation of the Src family protein-tyrosine kinase, Hck
    Huihui Ye
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1240 Biomedical Science Tower, Pittsburgh, Pennsylvania 15261, USA
    Biochemistry 43:15775-84. 2004
    ..Previous studies have shown that Nef, an HIV-1 accessory protein essential for AIDS progression, binds and activates Hck through its SH3 domain...
  37. ncbi Leucine-specific, functional interactions between human immunodeficiency virus type 1 Nef and adaptor protein complexes
    Scott H Coleman
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0679, USA
    J Virol 79:2066-78. 2005
    The human immunodeficiency virus type 1 virulence protein Nef interacts with the endosomal sorting machinery via a leucine-based motif...
  38. ncbi HIV-1 Nef impairs MHC class II antigen presentation and surface expression
    P Stumptner-Cuvelette
    Institut National de la Santé et de la Recherche Médicale U520 and Centre National de la Recherche Scientifique UMR144, Institut Curie, 75005 Paris, France
    Proc Natl Acad Sci U S A 98:12144-9. 2001
    HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated down-regulation of surface MHC I...
  39. ncbi Modulation of specific surface receptors and activation sensitization in primary resting CD4+ T lymphocytes by the Nef protein of HIV-1
    Oliver T Keppler
    Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
    J Leukoc Biol 79:616-27. 2006
    The human immunodeficiency virus type 1 (HIV-1) pathogenicity factor Nef increases viral replication in vivo. In immortalized cell lines, Nef affects the cell surface levels of multiple receptors and signal transduction pathways...
  40. ncbi Multiple human immunodeficiency virus type 1 Nef functions contribute to efficient replication in primary human macrophages
    Amanda Brown
    Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, 7th Floor, New York, NY 10016, USA
    J Gen Virol 85:1463-9. 2004
    The human immunodeficiency virus type 1 (HIV-1) Nef protein has been shown to accelerate viral growth kinetics in primary human T-lymphocytes and macrophages; however, the specific function(s) of Nef responsible for this phenotype in ..
  41. ncbi Human immunodeficiency virus type 1 Nef activates p21-activated kinase via recruitment into lipid rafts
    Ellen Krautkrämer
    Abteilung Virologie, Universitatsklinikum Heidelberg, D 69120 Heidelberg, Germany
    J Virol 78:4085-97. 2004
    The Nef protein of human immunodeficiency virus type 1 is an important factor in AIDS pathogenesis...
  42. ncbi HIV-1 Nef interacts with inositol trisphosphate receptor to activate calcium signaling in T cells
    Aki Manninen
    Institute of Medical Technology, University of Tampere, Tampere FIN 33014, Finland
    J Exp Med 195:1023-32. 2002
    HIV-1 pathogenicity factor Nef has been shown to modulate calcium signaling in host cells, but the underlying molecular mechanisms have remained unclear...
  43. ncbi HIV-1 Nef enhances both membrane expression and virion incorporation of Env products. A model for the Nef-dependent increase of HIV-1 infectivity
    Ilaria Schiavoni
    Laboratory of Virology, Istituto Superiore di Sanita, Rome, 00161 Italy
    J Biol Chem 279:22996-3006. 2004
    The expression of human immunodeficiency virus Nef increases the viral infectivity through mechanisms still not fully elucidated...
  44. ncbi Extracellular Nef protein targets CD4+ T cells for apoptosis by interacting with CXCR4 surface receptors
    Cleve O James
    Department of Microbiology Immunology Biochemistry Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA
    J Virol 78:3099-109. 2004
    The effects of soluble Nef protein on CD4(+) T cells were examined...
  45. ncbi Nef-mediated lipid raft exclusion of UbcH7 inhibits Cbl activity in T cells to positively regulate signaling
    Alison Simmons
    MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
    Immunity 23:621-34. 2005
    Lentiviral Nef increases T cell signaling activity, but the molecular nature of the stimulus involved is incompletely described. We explored CD4 T cell lipid raft composition in the presence and absence of Nef...
  46. ncbi HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane
    Vanessa Witte
    Department of Dermatology, University of Erlangen Nurnberg, 91052 Erlangen, Germany
    Mol Cell 13:179-90. 2004
    The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane...
  47. ncbi Nef-mediated downregulation of CD4 enhances human immunodeficiency virus type 1 replication in primary T lymphocytes
    Christopher A Lundquist
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2363, USA
    J Virol 76:4625-33. 2002
    The accessory protein Nef plays a crucial role in primate lentivirus pathogenesis. Nef enhances human immunodeficiency virus type 1 (HIV-1) infectivity in culture and stimulates viral replication in primary T cells...
  48. ncbi HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway
    S A Swann
    Departments of Medicine and Microbiology and Immunology, The University of Michigan, Ann Arbor, Michigan 48109, USA
    Virology 282:267-77. 2001
    HIV causes a chronic infection by evading immune eradication. A key element of HIV immune escape is the HIV-1 Nef protein...
  49. ncbi Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein
    T M Ross
    Yerkes Regional Primate Research Center, Division of Microbiology and Immunology, Emory University, Atlanta, Georgia 30329, USA
    Curr Biol 9:613-21. 1999
    The human immunodeficiency virus type 1 (HIV-1) Nef protein is required for efficient virus replication in vivo and displays a number of distinct and apparently unrelated biological activities in vitro...
  50. ncbi A basic patch on alpha-adaptin is required for binding of human immunodeficiency virus type 1 Nef and cooperative assembly of a CD4-Nef-AP-2 complex
    Rittik Chaudhuri
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Building 18T, Room 101, National Institutes of Health, Bethesda, MD 20892, USA
    J Virol 83:2518-30. 2009
    A critical function of the human immunodeficiency virus type 1 Nef protein is the downregulation of CD4 from the surfaces of infected cells...
  51. ncbi CD4 down-modulation by human immunodeficiency virus type 1 Nef correlates with the efficiency of viral replication and with CD4(+) T-cell depletion in human lymphoid tissue ex vivo
    S Glushakova
    The Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Virol 75:10113-7. 2001
    The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important virulence factor...
  52. ncbi Mechanism of Nef-induced CD4 endocytosis: Nef connects CD4 with the mu chain of adaptor complexes
    V Piguet
    Department of Genetics and Microbiology, Centre Medical Universitaire, 1, rue Michel Servet, 1211 Geneve 4, Switzerland
    EMBO J 17:2472-81. 1998
    The Nef protein of primate lentiviruses down-regulates the cell surface expression of CD4 and probably MHC I by connecting these receptors with the endocytic machinery...
  53. ncbi Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules
    S Le Gall
    Laboratoire Rétrovirus et Transfert Génétique Unité de Recherche Associée CNRS 1157, Institut Pasteur, Paris, France
    Immunity 8:483-95. 1998
    The surface expression of MHC I is reduced in HIV-infected cells. We show that the Nef protein affects the intracellular sorting of HLA-A and -B molecules...
  54. ncbi Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity
    H M Craig
    Department of Medicine, University of California at San Diego, La Jolla, CA 92093 0679, USA
    Proc Natl Acad Sci U S A 95:11229-34. 1998
    The HIV-1 Nef protein is important for pathogenesis, enhances viral infectivity, and regulates the sorting of at least two cellular transmembrane proteins, CD4 and major histocompatibility complex (MHC) class I...
  55. ncbi RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef
    S Arold
    Centre de Biochimie Structurale, UMR C9955 CNRS, U414 INSERM, Universite Montpellier 1, France
    Biochemistry 37:14683-91. 1998
    ..The RT loop has been shown to form a major part of the binding interface between SH3 domains and HIV-1 Nef. Thermodynamic data, derived from isothermal titration calorimetry, for the binding of Hck SH3 to HIV-1 Nef show ..
  56. ncbi Allosteric loss-of-function mutations in HIV-1 Nef from a long-term non-progressor
    Ronald P Trible
    Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Mol Biol 374:121-9. 2007
    Activation of Src family kinases by human immunodeficiency virus type 1 (HIV-1) Nef may play an important role in the pathogenesis of HIV/AIDS...
  57. ncbi The dileucine-based sorting motif in HIV-1 Nef is not required for down-regulation of class I MHC
    N L Riggs
    Department of Medicine, University of California, San Diego, CA, USA
    Virology 258:203-7. 1999
    ..protein sorting motif has recently been identified within the C-terminal, solvent-exposed loop of HIV-1 Nef and has been shown to be required for Nef-mediated down-regulation of CD4 and for optimal viral infectivity...
  58. ncbi Novel (n)PKC kinases phosphorylate Nef for increased HIV transcription, replication and perinuclear targeting
    Dietlinde Wolf
    University of Miami, Miller School of Medicine, Department of Microbiology and Immunology, BCRI 739, Miami, FL 33136, USA
    Virology 370:45-54. 2008
    The N-terminus of the human immunodeficiency virus (HIV) pathogenicity factor Nef associates with a protein complex (NAKC for Nef-associated kinase complex) that contains at least two kinases: the tyrosine kinase Lck and a serine kinase ..
  59. ncbi HIV-1 Nef increases T cell activation in a stimulus-dependent manner
    J A Schrager
    Laboratory of Molecular Biology, National Institute of Mental Health, 36 Convent Drive, Bethesda, MD 20892 4034, USA
    Proc Natl Acad Sci U S A 96:8167-72. 1999
    Lentiviral Nef increases viral replication in vivo, plays a direct role in pathogenesis, and increases viral particle infectivity...
  60. ncbi CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef
    B K Chen
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    J Virol 70:6044-53. 1996
    The human immunodeficiency virus type 1 (HIV-1) genes vpu, env, and nef have all been implicated in modulating the levels of cell surface CD4 on infected cells...
  61. ncbi The human thioesterase II protein binds to a site on HIV-1 Nef critical for CD4 down-regulation
    G B Cohen
    AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 275:23097-105. 2000
    A HIV-1 Nef affinity column was used to purify a 35-kDa Nef-interacting protein from T-cell lysates...
  62. ncbi Human immunodeficiency virus type 1 Nef selectively associates with a catalytically active subpopulation of p21-activated kinase 2 (PAK2) independently of PAK2 binding to Nck or beta-PIX
    G H Renkema
    Institute of Medical Technology, University of Tampere, Tampere, Finland
    J Virol 75:2154-60. 2001
    We have recently identified the Nef-associated serine-threonine kinase (NAK) as the p21-activated kinase 2 (PAK2)...
  63. ncbi Nef mutations in long-term non-progressors from former plasma donors infected with HIV-1 subtype B in China
    Shu Hua Wang
    State Key Laboratory for Infection Diseases Prevention and Control, National Center for AIDS STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China
    Biomed Environ Sci 21:485-91. 2008
    To study the specific amino acid variation in Nef that may be related to disease progression after infection with HIV-1 subtype B, a predominant strain circulating in China, and to determine whether changes in Nef secondary structure may ..
  64. ncbi Lentivirus vectors expressing short hairpin RNAs against the U3-overlapping region of HIV nef inhibit HIV replication and infectivity in primary macrophages
    Takuya Yamamoto
    Department of Immunology, National Institute of Infectious Diseases, Toyama 1 23 1, Shinjuku ku, Tokyo 162 8640, Japan
    Blood 108:3305-12. 2006
    ..In this study, we identified a putative RNAi target of HIV, consisting of the portion of the nef gene overlapping the U3 region (Nef366), and generated a lentivirus-based short hairpin RNA (shRNA) expression ..
  65. ncbi Nef induces apoptosis by activating JNK signaling pathway and inhibits NF-kappaB-dependent immune responses in Drosophila
    Sung Bae Lee
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305 701, Korea
    J Cell Sci 118:1851-9. 2005
    The human immunodeficiency virus type 1 (HIV-1) nef gene encodes a 27-kDa protein that plays a crucial role during AIDS pathogenesis, but its exact functional mechanism has not been fully elucidated and remains controversial...
  66. ncbi Constitutive activation of phosphatidylinositol 3-kinase signaling pathway down-regulates TLR4-mediated tumor necrosis factor-alpha release in alveolar macrophages from asymptomatic HIV-positive persons in vitro
    Souvenir D Tachado
    Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 283:33191-8. 2008
    ..Incubation of human macrophages with exogenous HIV Nef protein induced phosphorylation of Akt and GSK-3beta (whereas phosphorylation was reduced by PI3K inhibition) and ..
  67. ncbi HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation
    Karuppiah Muthumani
    University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine 422 Curie Blvd, Philadelphia, PA 19104, USA
    Blood 106:2059-68. 2005
    ..is manifested in part through up-regulation of the death receptor Fas ligand (FasL) by HIV-1 negative factor (Nef), leading to bystander damage...
  68. ncbi Functional characterization of the human immunodeficiency virus type 1 Nef acidic domain
    Laura L Baugh
    Y9 206, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    J Virol 82:9657-67. 2008
    The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef downregulates major histocompatibility complex class I (MHC-I) from the cell surface...
  69. ncbi Alterations in intracellular potassium concentration by HIV-1 and SIV Nef
    Bongkun Choi
    Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
    Virol J 5:60. 2008
    ..Xenopus laevis oocytes have few functional endogenous ion channels, and have proven useful as a system to examine direct effects of exogenously added proteins on ion transport...
  70. ncbi Genetic characterization of HIV type 1 Nef-induced vesicle secretion
    Syed A Ali
    Department of Microbiology, Morehouse School of Medicine, Atlanta, GA 30310, USA
    AIDS Res Hum Retroviruses 26:173-92. 2010
    The HIV-1 Nef protein is known to be secreted, and our group has shown that Nef is secreted from nef-transfected and HIV-1-infected cells in small exosome-like vesicles (d. 40-100 nm)...
  71. ncbi The cell biology of HIV-1 and other retroviruses
    Eric O Freed
    Virus Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702 1201, USA
    Retrovirology 3:77. 2006
    ..MEETING REPORT: The conference began with a keynote address from W. Sundquist on the biochemistry of HIV-1 budding. This presentation will be described in the section on Assembly and Release of Retroviruses...
  72. ncbi Mapping the binding site of full length HIV-1 Nef on human Lck SH3 by NMR spectroscopy
    Lars Briese
    Institut fur Molekulare Biotechnologie, 07745, Jena, Germany
    J Biomed Sci 12:451-6. 2005
    The Nef protein of human immunodeficiency virus type 1 (HIV-1) is known to directly bind to the SH3 domain of human lymphocyte specific kinase (Lck) via a proline-rich region located in the amino terminal part of Nef...
  73. ncbi Modelling thymic HIV-1 Nef effects
    Veronique Stove
    Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent University Hospital, 9000 Ghent, Belgium
    Curr HIV Res 4:57-64. 2006
    The nef gene is conserved among primate lentiviruses and is one of the first viral genes that is transcribed following infection...
  74. ncbi Possible role of deep tubular invaginations of the plasma membrane in MHC-I trafficking
    Ramiro H Massol
    Department of Cell Biology and The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Exp Cell Res 306:142-9. 2005
    ..Expression of NefAAAA, a mutant form of HIV Nef, increases the number of cells containing the stable tubules, and is used here as a tool to facilitate their study...
  75. ncbi HIV-1 Nef-mediated inhibition of T cell migration and its molecular determinants
    In Woo Park
    Center for AIDS Research and Department of Microbiology and Immunology, Indiana University School of Medicine, R2 302, 950 W Walnut St, Indianapolis, IN 46202, USA
    J Leukoc Biol 86:1171-8. 2009
    ..Previous studies have shown that HIV-1 Nef inhibits T cell chemotaxis in response to the physiological ligand SDF-1alpha [( 1) ]...
  76. ncbi Phosphorylation of HIV Nef by cAMP-dependent protein kinase
    Pei Lin Li
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Virology 331:367-74. 2005
    b>Nef, a multifunctional accessory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), is important for disease progression...
  77. ncbi Affinity of Src family kinase SH3 domains for HIV Nef in vitro does not predict kinase activation by Nef in vivo
    S D Briggs
    Eppley Institute for Research in Cancer and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    Biochemistry 39:489-95. 2000
    b>Nef is an HIV accessory protein required for high-titer viral replication and AIDS progression...
  78. ncbi Induction of interleukin-15 production by HIV-1 nef protein: a role in the proliferation of uninfected cells
    M G Quaranta
    Department of Immunology, Istituto Superiore di Sanita, Rome, Italy
    Exp Cell Res 250:112-21. 1999
    Several recent reports have provided evidence that Nef enhances human immunodeficiency virus HIV infectivity, and in vitro experiments with the nef gene have demonstrated the possible role of Nef in modulating immune responses...
  79. ncbi Regulation of human immunodeficiency virus type 1 infectivity by the ERK mitogen-activated protein kinase signaling pathway
    X Yang
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Virol 73:3460-6. 1999
    ..The HIV-1 Rev, Tat, p17(Gag), and Nef proteins were directly phosphorylated by MAPK in vitro, suggesting that other HIV-1 proteins are potential ..
  80. ncbi T cells chronically infected with HIV do not contain sufficient Nef to promote CD4 downmodulation in the absence of envelope-mediated effects
    M Cucchiarini
    Laboratoire de Virologie, Faculte de Medecine, Nice, France
    J Acquir Immune Defic Syndr Hum Retrovirol 17:112-9. 1998
    Among HIV viral proteins, envelope glycoproteins and Nef have been both suggested to participate in CD4 downregulation during the course of HIV infection...
  81. ncbi The HIV-1 nef protein inhibits extracellular signal-regulated kinase-dependent DNA synthesis in a human astrocytic cell line
    I A Romero
    CNRS UPR 0415, Institut Cochin de Genetique Moleculaire, Paris, France
    J Neurochem 70:778-85. 1998
    ..infection of astrocytes by human immunodeficiency virus type 1 (HIV-1), characterized by the overexpression of nef, in brain disease progression is largely unknown...
  82. ncbi A novel acyl-CoA thioesterase enhances its enzymatic activity by direct binding with HIV Nef
    H Watanabe
    Division of Molecular Genetics, Chiba University School of Medicine, Japan
    Biochem Biophys Res Commun 238:234-9. 1997
    In addition to playing a crucial role in the pathogenesis of AIDS, HIV nef induces down-regulation of CD4 expression and TCR signaling and also regulates the sorting pathway in host T cells...
  83. ncbi Expression of HIV-1 nef decreases basal phosphatidyl-inositol 3-kinase activity
    A Garcia
    Groupe de développement cellulaire et unité d immunologie virale, Institut Pasteur, Paris, France
    C R Acad Sci III 320:505-8. 1997
    CEM lymphoid cells expressing high levels of HIV-1 nef protein displayed a significant decrease in basal phosphatidyl-inositol 3-kinase (P13-kinase) activity associated with immunoprecipitates with anti-p85 regulatory subunit...
  84. ncbi Protein kinase C-mediated phosphorylation of HIV-I nef in human cell lines
    K Coates
    MRC Retrovirus Research Laboratory, Department of Veterinary Pathology, University of Glasgow, Glasgow G61 1QH, Scotland, United Kingdom
    J Biol Chem 272:12289-94. 1997
    Stable human cell lines expressing the human immunodeficiency virus type I (HIV-I) Nef protein from inducible promoters were used to analyze the phosphorylation status of Nef in vivo...
  85. ncbi The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase
    S Grzesiek
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Struct Biol 3:340-5. 1996
    The solution structure of HIV-1 Nef has been solved by multidimensional heteronuclear NMR spectroscopy...
  86. ncbi The negative effect of human immunodeficiency virus type 1 Nef on cell surface CD4 expression is not species specific and requires the cytoplasmic domain of CD4
    J V Garcia
    Department of Virology and Molecular Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105
    J Virol 67:1511-6. 1993
    The nef gene product of human immunodeficiency virus type 1 has been shown to induce CD4 downregulation from the surface of human cells...
  87. ncbi Myristoylation-dependent binding of HIV-1 Nef to CD4
    M P Harris
    Department of Veterinary Pathology, University of Glasgow, Scotland, U K
    J Mol Biol 241:136-42. 1994
    The nef gene is conserved throughout the primate lentivirus family. Although dispensable in vitro, an important role for nef in vivo is suggested by the failure of SIV nef mutants to establish persistent viraemia...
  88. ncbi Human immunodeficiency virus type 1 Nef induces accumulation of CD4 in early endosomes
    O Schwartz
    Laboratoire Rétrovirus et Transfert Génétique URA CNRS 1157, Paris, France
    J Virol 69:528-33. 1995
    We have studied the fate of CD4 in CEM T cells expressing a human immunodeficiency virus type 1 HIV-1 Nef protein. Nef triggered a rapid endocytosis and a degradation of CD4, while most of the p56lck was upheld at the cell membrane...
  89. ncbi Human immunodeficiency virus type 1 Nef mediates sustained membrane expression of tumor necrosis factor and the related cytokine LIGHT on activated T cells
    J Lama
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Virol 74:9396-402. 2000
    Human immunodeficiency virus (HIV) Nef downregulates the antigen recognition molecules major histocompatibility complex class I and CD4...
  90. ncbi Lentivirus Nef specifically activates Pak2
    V K Arora
    Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Virol 74:11081-7. 2000
    b>Nef proteins from human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have been found to associate with an active cellular serine/threonine kinase designated Nef-associated kinase (Nak)...
  91. ncbi Modulation of CD8 and CD3 by HIV or HIV antigens
    J Jason
    Mailstop A 25, Immunology Branch, DASTLR NCID, Centers for Disease Control and Prevention, Department of Health and Human Services, Public Health Service, 1600 Clifton Road NE, Atlanta, GA 30333, USA
    Scand J Immunol 53:259-67. 2001
    ..phytohaemagglutinin (PHA)-stimulated, PHA/HIV-inoculated (PHA/HIV), or placed into media with soluble gp120, Rev or Nef. HIV inoculation and Nef had striking modulatory effects on CD8...
  92. ncbi Nef-induced alteration of the early/recycling endosomal compartment correlates with enhancement of HIV-1 infectivity
    Ricardo Madrid
    Institut Cochin, Department of Infectious Diseases, INSERM U567, CNRS UMR8104, Universite Paris 5, 75014 Paris, France
    J Biol Chem 280:5032-44. 2005
    human immunodeficiency virus type 1 (HIV-1) Nef interacts with the clathrin-associated AP-1 and AP-3 adaptor complexes, stabilizing their association with endosomal membranes...
  93. ncbi HIV-1 Nef promotes survival of TF-1 macrophages by inducing Bcl-XL expression in an extracellular signal-regulated kinase-dependent manner
    Hyun Jung Choi
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 279:51688-96. 2004
    The Nef protein of human immunodeficiency virus-1 (HIV-1) is essential for the progression from human and simian immunodeficiency virus infection to full-blown AIDS...
  94. ncbi ARF1 regulates Nef-induced CD4 degradation
    Julien Faure
    Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland
    Curr Biol 14:1056-64. 2004
    The HIV Nef protein downregulates CD4 through sequential connection with clathrin-coated pits and the COP1 coatomer, resulting in accelerated endocytosis and lysosomal targeting.
  95. ncbi HIV type 1 Nef increases the association of T cell receptor (TCR)-signaling molecules with T cell rafts and promotes activation-induced raft fusion
    Julianne T Djordjevic
    Institute for Immunology and Allergy Research, Westmead Millennium Institute, NSW 2145, Australia
    AIDS Res Hum Retroviruses 20:547-55. 2004
    HIV-1 Nef (Nef) is a myristoylated protein that contributes to HIV disease pathogenesis. Nef has a modulatory effect on T cell receptor (TCR) signaling, resulting in up-regulation of interleukin-2 (IL-2) production in stimulated T cells...
  96. ncbi The functional consequences of delivery of HIV-1 Nef to dendritic cells using an adenoviral vector
    Luci P MacCormac
    Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, W1T 4JF London, UK
    Vaccine 22:528-35. 2004
    The Nef gene is a major determinant of HIV-1 pathogenicity...
  97. ncbi Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB
    Anna L Lahti
    Institute of Medical Technology, FIN 33014 University of Tampere, Tampere, Finland
    Virology 310:190-6. 2003
    b>Nef and Vpr are lentiviral accessory proteins that have been implicated in regulation of cellular gene expression...
  98. ncbi Coxiella burnetii avoids macrophage phagocytosis by interfering with spatial distribution of complement receptor 3
    Christian Capo
    Unite des Rickettsies, Faculte de Medecine, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6020, Marseille, France
    J Immunol 170:4217-25. 2003
    ..In addition, monocyte activation due to the expression of HIV-1 Nef protein also restored CR3-mediated phagocytosis of C...
  99. ncbi Nef protein of human immunodeficiency virus and lipopolysaccharide induce expression of CD14 on human monocytes through differential utilization of interleukin-10
    David Creery
    Department of Pediatrics, Children s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
    Clin Diagn Lab Immunol 9:1212-21. 2002
    ..effects of cytokines, the bacterial product lipopolysaccharide (LPS), and/or the HIV regulatory antigens Tat and Nef. Interleukin-10 (IL-10), an immunoregulatory cytokine, as well as LPS enhanced mCD14 expression and the release of ..
  100. ncbi Effects of HIV-1 Nef on cellular gene expression profiles
    Syed Shaheduzzaman
    HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Biomed Sci 9:82-96. 2002
    The early human immunodeficiency virus (HIV) accessory protein Nef makes an important contribution to virulence, but the mechanisms by which Nef influences pathogenesis remain unclear...
  101. ncbi Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement
    I Moarefi
    Laboratories of Molecular Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York 10021, USA
    Nature 385:650-3. 1997
    ..We show that addition of the HIV-1 Nef protein, which is a high-affinity ligand for the Hck SH3 domain, to either the downregulated or activated form of ..

Research Grants62

  1. HIV-1 Vpu and BST-2/CD317
    John Guatelli; Fiscal Year: 2010
    ..The HIV-1 protein Vpu counteracts this host defense. This research is designed to explore how BST-2 retains virus particles, how Vpu antagonizes this activity, and how BST-2 is regulated within primary cells of the immune system. ..
  2. The MHC-I, HIV-1 Nef, AP-1 Complex
    John Guatelli; Fiscal Year: 2007
    Immune evasion by HIV-1 involves modulation of class I MHC glycoproteins by Nef. Antigen presentation by infected cells is inhibited due to misrouting of MHC-I from the cell surface to the endo-lysosomal system...
  3. Role of specific Nef functions in AIDS pathogenesis
    Frank Kirchhoff; Fiscal Year: 2007
    We propose that the inability of the accessory HIV-1 Nef protein to inhibit T cell activation and apoptosis contributes to the high levels of immune activation and accelerates progression to AIDS...
  4. HIV 1 NEF AND VIRAL INFECTIVITY
    John Guatelli; Fiscal Year: 2007
    HIV-1 Nef is an important virulence factor that down-regulates CD4 and class I MHC from the cell surface and enhances viral infectivity and replication...
  5. PROTEIN PROFILING OF ORAL MUCOSA OF HIV TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2007
    ..Aim 5-To identify the specific Nef-expressing cells of CD4C/HIV Tg mice associated with specific changes in protein profiles of oral mucosa...
  6. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2007
    ..abstract_text> ..
  7. Factors/HIV-1 Nef's Ability to Direct Immune Evasion
    Martha Lewis; Fiscal Year: 2007
    ..The plan focuses on investigating factors influencing the HIV-1 accessory protein Nef's ability to mediate evasion of CTL immune responses. Previous studies by Dr...
  8. Role of HIPK2 in Kidney Tubulointerstitial Injury
    AVI MA apos AYAN; Fiscal Year: 2010
    ....
  9. HIV-1 Vpu and BST-2/CD317
    John Guatelli; Fiscal Year: 2011
    ..The HIV-1 protein Vpu counteracts this host defense. This research is designed to explore how BST-2 retains virus particles, how Vpu antagonizes this activity, and how BST-2 is regulated within primary cells of the immune system. ..
  10. HIV 1 NEF AND VIRAL INFECTIVITY
    John Guatelli; Fiscal Year: 2010
    HIV-1 Nef enhances the infectivity of cell-free virions by an incompletely understood process. The research proposed here is designed to continue an ongoing investigation of how Nef enhances viral infectivity...
  11. Structure Based Themodynamic Studies of HIV-1 Protease
    Ernesto Freire; Fiscal Year: 2010
    ....
  12. HIV-1 Vpu and BST-2/CD317
    John Guatelli; Fiscal Year: 2009
    ..The HIV-1 protein Vpu counteracts this host defense. This research is designed to explore how BST-2 retains virus particles, how Vpu antagonizes this activity, and how BST-2 is regulated within primary cells of the immune system. ..
  13. Cellular and molecular mechanism of retinoids in podocytes
    John C He; Fiscal Year: 2010
    ..Our study may lead to discover new targets of intervention for glomerular diseases and identify new therapy regimes of retinoids by enhancing its beneficial effects and reducing its side effects in patients with kidney diseases. ..
  14. HIV-1 Nef's Role in Pathogenesis in vivo
    Martha J Lewis; Fiscal Year: 2010
    The projects proposed in this application aim to expand our understanding of how the Nef protein of HIV functions in vivo to promote viral persistence...
  15. HIV Compromises Lung Macrophage TLR Host Defense Function
    Souvenir D Tachado; Fiscal Year: 2010
    ..3) To identify HIV-derived (Nef, gp120, ssRNA) and host-derived (IL-10) factors that contribute to HIV-mediated immune dysregulation in response to ..
  16. PROTEIN PROFILING OF ORAL MUCOSA OF HIV TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2010
    ..Aim 5-To identify the specific Nef-expressing cells of CD4C/HIV Tg mice associated with specific changes in protein profiles of oral mucosa...
  17. Cellular and molecular mechanism of retinoids in podocytes
    JOHN HE; Fiscal Year: 2009
    ..Our study may lead to discover new targets of intervention for glomerular diseases and identify new therapy regimes of retinoids by enhancing its beneficial effects and reducing its side effects in patients with kidney diseases. ..
  18. HIV-1 Vpu and BST-2/CD317
    John Guatelli; Fiscal Year: 2010
    ..The HIV-1 protein Vpu counteracts this host defense. This research is designed to explore how BST-2 retains virus particles, how Vpu antagonizes this activity, and how BST-2 is regulated within primary cells of the immune system. ..
  19. STUDIES OF LUNG DISEASES OF HIV TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2009
    ..1- To determine whether the development of the lung disease of CD4C/HIV Tg mice is caused by expression of HIV-1 Nef in cells of the immune system or in other cells...
  20. CARDIAC LESIONS IN HIV1 TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2001
    ..End of Abstract) ..
  21. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2005
    ....
  22. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2004
    ....
  23. CHEMOKINES IN LUNG DISEASE OF HIV1 TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2003
    ..4- To determine whether blocking or deleting specific chemokines or their receptors and overexpressing some chemokine receptors alter the development of lymphocytic interstitial pneumonitis. ..
  24. PATHOGENIC CONVERSION OF ATTENUATED SIV VACCINES
    Earl Sawai; Fiscal Year: 2003
    ..Such studies in juvenile and adult macaques revealed that viral accessory genes, including nef, are important for pathogenesis...