nef

Summary

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

Top Publications

  1. doi Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses
    Frank Kirchhoff
    Institute of Molecular Virology, University Hospital Ulm, Meyerhofstrasse 1, 89081 Ulm, Germany
    Cell Host Microbe 8:55-67. 2010
  2. doi HIV-1 accessory proteins--ensuring viral survival in a hostile environment
    Michael H Malim
    Department of Infectious Diseases, King s College London School of Medicine, 2nd Floor, Borough Wing, Guy s Hospital, London Bridge, London, SE1 9RT, UK
    Cell Host Microbe 3:388-98. 2008
  3. pmc 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
  4. pmc HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells
    Metka Lenassi
    Departments of Medicine, Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA
    Traffic 11:110-22. 2010
  5. pmc Secretion modification region-derived peptide disrupts HIV-1 Nef's interaction with mortalin and blocks virus and Nef exosome release
    Martin N Shelton
    Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, USA
    J Virol 86:406-19. 2012
  6. 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
  7. ncbi Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain
    C H Lee
    The Rockefeller University, New York, New York 10021, USA
    Cell 85:931-42. 1996
  8. pmc Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions
    Yong Hui Zheng
    Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143 0703, USA
    Proc Natl Acad Sci U S A 100:8460-5. 2003
  9. pmc Mechanisms of HIV-1 Nef function and intracellular signaling
    John L Foster
    Division of Infectious Diseases, Center for AIDS Research, Chapel Hill, NC 27599 7042, USA
    J Neuroimmune Pharmacol 6:230-46. 2011
  10. pmc 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

Research Grants

  1. CARDIAC LESIONS IN HIV1 TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2001
  2. CHEMOKINES IN LUNG DISEASE OF HIV1 TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2003
  3. PROTEIN PROFILING OF ORAL MUCOSA OF HIV TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2010
  4. STUDIES OF LUNG DISEASES OF HIV TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2009
  5. Selective Inhibitors of SRC Family Kinases in Neoplasia
    THOMAS SMITHGALL; Fiscal Year: 2002
  6. Src Family Kinases as Molecular Targets for HIV/Nef
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
  7. Cytoplasmic Tyrosine Kinase Pathways and ES Cell Fate
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
  8. Targeting HIV-1 Nef with Small Molecules
    THOMAS SMITHGALL; Fiscal Year: 2008
  9. Pathogenesis of HIVAN: the role of Nef
    JOHN HE; Fiscal Year: 2007
  10. Src Family Tyrosine Kinases in Tumor Cell Signaling
    THOMAS SMITHGALL; Fiscal Year: 2007

Detail Information

Publications204 found, 100 shown here

  1. doi Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses
    Frank Kirchhoff
    Institute of Molecular Virology, University Hospital Ulm, Meyerhofstrasse 1, 89081 Ulm, Germany
    Cell Host Microbe 8:55-67. 2010
    ..Here, I summarize some of our current knowledge on the acquisition and function of the viral vif, vpr, vpu, and nef genes, with a particular focus on the evolution and specific properties of pandemic HIV-1 strains that may ..
  2. doi HIV-1 accessory proteins--ensuring viral survival in a hostile environment
    Michael H Malim
    Department of Infectious Diseases, King s College London School of Medicine, 2nd Floor, Borough Wing, Guy s Hospital, London Bridge, London, SE1 9RT, UK
    Cell Host Microbe 3:388-98. 2008
    ..Here, we discuss recent advances in understanding the interactions of the HIV-1 Nef, Vif, Vpu, and Vpr proteins with factors and pathways expressed in cells of the immune system...
  3. pmc 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...
  4. pmc HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells
    Metka Lenassi
    Departments of Medicine, Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA
    Traffic 11:110-22. 2010
    The HIV accessory protein negative factor (Nef) is one of the earliest and most abundantly expressed viral proteins. It is also found in the serum of infected individuals (Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C...
  5. pmc Secretion modification region-derived peptide disrupts HIV-1 Nef's interaction with mortalin and blocks virus and Nef exosome release
    Martin N Shelton
    Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, USA
    J Virol 86:406-19. 2012
    b>Nef is secreted from infected cells in exosomes and is found in abundance in the sera of HIV-infected individuals...
  6. 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 ..
  7. ncbi Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain
    C H Lee
    The Rockefeller University, New York, New York 10021, USA
    Cell 85:931-42. 1996
    The crystal structure of the conserved core of HIV-1 Nef has been determined in complex with the SH3 domain of a mutant Fyn tyrosine kinase (a single amino acid substitution, Arg-96 to isoleucine), to which Nef binds tightly...
  8. pmc Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions
    Yong Hui Zheng
    Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143 0703, USA
    Proc Natl Acad Sci U S A 100:8460-5. 2003
    HIV buds from lipid rafts and requires cholesterol for its egress from and entry into cells. Viral accessory protein Nef plays a major role in this process...
  9. pmc Mechanisms of HIV-1 Nef function and intracellular signaling
    John L Foster
    Division of Infectious Diseases, Center for AIDS Research, Chapel Hill, NC 27599 7042, USA
    J Neuroimmune Pharmacol 6:230-46. 2011
    Advances in the last several years have enhanced mechanistic understanding of Nef-induced CD4 and MHCI downregulation and have suggested a new paradigm for analyzing Nef function...
  10. pmc 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...
  11. pmc Human immunodeficiency virus impairs reverse cholesterol transport from macrophages
    Zahedi Mujawar
    The George Washington University, Washington, District of Columbia, USA
    PLoS Biol 4:e365. 2006
    ..In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells...
  12. ncbi SH3-Domain binding function of HIV-1 Nef is required for association with a PAK-related kinase
    A Manninen
    Institute of Medical Technology, University of Tampere, Tampere, FIN 33101, Finland
    Virology 250:273-82. 1998
    HIV-1 Nef has previously been shown to bind to Src homology-3 (SH3) domains of a subset of Src family tyrosine kinases...
  13. pmc Mutation of a conserved residue (D123) required for oligomerization of human immunodeficiency virus type 1 Nef protein abolishes interaction with human thioesterase and results in impairment of Nef biological functions
    L X Liu
    Institut Cochin de Genetique Moleculaire, INSERM U 529 Université Paris V, 75014 Paris, France
    J Virol 74:5310-9. 2000
    b>Nef is a myristoylated protein of 27 to 35 kDa that is conserved in primate lentiviruses. In vivo, Nef is required for high viral load and full pathological effects...
  14. pmc Mechanism for down-regulation of CD28 by Nef
    T Swigut
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    EMBO J 20:1593-604. 2001
    SIV and HIV Nef proteins disrupt T-cell receptor machinery by down-modulating cell surface expression of CD4 and expression or signaling of CD3-TCR...
  15. ncbi Induction of HIV transcription by Nef involves Lck activation and protein kinase C theta raft recruitment leading to activation of ERK1/2 but not NF kappa B
    Vanessa Witte
    Otto von Guericke University of Magdeburg, Institute of Molecular and Clinical Immunology, Magdeburg, Germany
    J Immunol 181:8425-32. 2008
    The Nef protein of HIV-1 is a key promoter of disease progression, owing to its dramatic yet ill-defined impact on viral replication...
  16. pmc Stimulation of the liver X receptor pathway inhibits HIV-1 replication via induction of ATP-binding cassette transporter A1
    Matthew P Morrow
    George Washington University, Washington DC, USA
    Mol Pharmacol 78:215-25. 2010
    ..Recently, we demonstrated that HIV-1, via its protein Nef, inhibits the activity of the major cellular cholesterol transporter ATP binding cassette transporter A1 (ABCA1), ..
  17. ncbi Human immunodeficiency virus type 1 Nef mediates activation of STAT3 in immature dendritic cells
    D Messmer
    North Shore LIJ Research Institute, Manhasset, New York 11030, USA
    AIDS Res Hum Retroviruses 18:1043-50. 2002
    ..of immunodeficiency viruses (HIV-1 and SIV) in immature dendritic cell (DC)-T cell cocultures is dependent on Nef. In contrast, mature DCs promote the replication of wild-type and nef-defective SIV in concert with CD4(+) T cells...
  18. 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...
  19. ncbi Vav exchange factor counteracts the HIV-1 Nef-mediated decrease of plasma membrane GM1 and NF-AT activity in T cells
    Loretta Tuosto
    Department of Cellular and Developmental Biology, La Sapienza University, Rome, Italy
    Eur J Immunol 33:2186-96. 2003
    ..Moreover, a functional link among lipid microdomains, Vav and the HIV product Nef has been described...
  20. ncbi Selective downmodulation of HLA-A and -B by Nef alleles from different groups of primate lentiviruses
    Anke Specht
    Institute of Virology, Universitatsklinikum, 89081 Ulm, Germany
    Virology 373:229-37. 2008
    It has been demonstrated that the HIV-1 NL4-3 and IIIB Nef alleles downregulate HLA-A and -B but not -C or -E from the cell surface...
  21. pmc An MHC-I cytoplasmic domain/HIV-1 Nef fusion protein binds directly to the mu subunit of the AP-1 endosomal coat complex
    Rajendra Kumar Singh
    Department of Medicine, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 4:e8364. 2009
    ..The down-regulation of the major histocompatibility complex class I (MHC-I) from the surface of infected cells by the Nef proteins of primate immunodeficiency viruses likely contributes to pathogenesis by providing evasion of cell-..
  22. doi The HIV-1 Nef protein has a dual role in T cell receptor signaling in infected CD4+ T lymphocytes
    Francesca Neri
    Laboratory of Immunoinfectivology, Children s Hospital Bambino Gesu, 00165 Rome, Italy
    Virology 410:316-26. 2011
    ..The pathogenic Nef protein of HIV-1 modulates the T cell receptor (TCR) signaling, but whether this has a positive or negative effect ..
  23. doi Conformation of the dileucine-based sorting motif in HIV-1 Nef revealed by intermolecular domain assembly
    Florian A Horenkamp
    Abteilung Physikalische Biochemie, Max Planck Institut fur molekulare Physiologie, Otto Hahn Strasse 11, 44227 Dortmund, Germany
    Traffic 12:867-77. 2011
    The human immunodeficiency virus 1 (HIV-1) Nef protein is a pathogenicity factor required for effective progression to AIDS, which modulates host cell signaling pathways and T-cell receptor internalization...
  24. pmc Nef-mediated enhancement of cellular activation and human immunodeficiency virus type 1 replication in primary T cells is dependent on association with p21-activated kinase 2
    Kevin C Olivieri
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA, USA
    Retrovirology 8:64. 2011
    The HIV-1 accessory protein Nef is an important determinant of lentiviral pathogenicity that contributes to disease progression by enhancing viral replication and other poorly understood mechanisms...
  25. doi Human immunodeficiency virus-1 Nef suppresses Hsp70-mediated Tat activation
    Ryuichi Sugiyama
    Department of Life and Environmental Sciences, Chiba Institute of Technology, 2 17 1 Tsudanuma, Narashino, Chiba 275 0016, Japan
    FEBS Lett 585:3367-71. 2011
    ..Although previous reports have indicated that HIV-1 Nef positively or negatively regulates HIV-1 gene expression, the precise molecular mechanisms by which this occurs ..
  26. doi HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling
    Xiaoyu Pan
    Department of Infectious Diseases, Virology, University Hospital Heidelberg, Germany
    Blood 119:786-97. 2012
    The Nef protein of HIV-1 facilitates viral replication and disease progression in vivo...
  27. pmc Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef
    Xiaofei Jia
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
    Nat Struct Mol Biol 19:701-6. 2012
    The HIV-1 protein Nef inhibits antigen presentation by class I major histocompatibility complex (MHC-I)...
  28. doi Nef does not inhibit F-actin remodelling and HIV-1 cell-cell transmission at the T lymphocyte virological synapse
    Claudia Haller
    Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
    Eur J Cell Biol 90:913-21. 2011
    b>Nef, a HIV-1 pathogenesis factor, elevates virus replication in vivo and thus progression to AIDS by incompletely defined mechanisms...
  29. pmc ADP ribosylation factor 1 activity is required to recruit AP-1 to the major histocompatibility complex class I (MHC-I) cytoplasmic tail and disrupt MHC-I trafficking in HIV-1-infected primary T cells
    Elizabeth R Wonderlich
    Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA
    J Virol 85:12216-26. 2011
    ..HIV-1-infected cells are partially resistant to anti-HIV cytotoxic T lymphocytes (CTLs) due to the effects of the HIV Nef protein on antigen presentation by major histocompatibility complex class I (MHC-I), and evidence has been ..
  30. pmc A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein
    C H Lee
    Laboratory of Molecular Biophysics, Rockefeller University, New York, NY 10021, USA
    EMBO J 14:5006-15. 1995
    We have examined the differential binding of Hck and Fyn to HIV-1 Nef to elucidate the structural basis of SH3 binding affinity and specificity...
  31. ncbi A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor
    P A Bresnahan
    Gladstone Institute of Virology and Immunology, University of California, San Francisco 94141, USA
    Curr Biol 8:1235-8. 1998
    Human immunodeficiency virus 1 (HIV-1) Nef downregulates surface expression of CD4, an integral component of the functional HIV receptor complex, through accelerated endocytosis of surface receptors and diminished transport of CD4 from ..
  32. pmc HIV-1 Nef disrupts the podocyte actin cytoskeleton by interacting with diaphanous interacting protein
    Ting Chi Lu
    Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Biol Chem 283:8173-82. 2008
    The ability of the human immunodeficiency virus, type 1 (HIV-1) protein Nef to induce cytoskeleton changes in infected host cells is a key event in viral replication...
  33. pmc 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...
  34. pmc 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...
  35. pmc Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo
    Stefanie Homann
    Department of Virology, University of Heidelberg, Germany
    Retrovirology 6:6. 2009
    HIV-1 Nef critically contributes to AIDS in part by augmenting virus titers in infected individuals...
  36. 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...
  37. ncbi Functional characterization of HIV-1 Nef mutants in the context of viral infection
    Oliver T Fackler
    Department of Virology, University of Heidelberg, INF 324, D 69120 Heidelberg, Germany
    Virology 351:322-39. 2006
    b>Nef is an important pathogenesis factor of HIV-1 with a multitude of effector functions...
  38. ncbi CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef
    Takamasa Ueno
    Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan
    J Immunol 180:1107-16. 2008
    HIV-1 Nef plays multiple roles in modulating immune responses, even though it is a dominant CTL target itself. How Nef accomplishes the balance between such conflicting selective pressures remains elusive...
  39. 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...
  40. pmc 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...
  41. 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...
  42. pmc 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 ..
  43. ncbi Synergistic activation of NFAT by HIV-1 nef and the Ras/MAPK pathway
    A Manninen
    Institute of Medical Technology, University of Tampere, P O Box 607, FIN 33101 and the Department of Clinical Chemistry, Tampere University Hospital, P O Box 2000, FIN 33521, Tampere, Finland
    J Biol Chem 275:16513-7. 2000
    b>Nef is a lentiviral protein involved in pathogenesis of AIDS, but its molecular mechanisms of action remain incompletely understood...
  44. ncbi SH3-dependent stimulation of Src-family kinase autophosphorylation without tail release from the SH2 domain in vivo
    Edwina C Lerner
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Nat Struct Biol 9:365-9. 2002
    ..Here we show that SH3-dependent activation of the Src family member Hck by HIV-1 Nef binding or by SH2-kinase linker mutation does not affect tail tyrosine phosphorylation in fibroblasts...
  45. 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...
  46. ncbi HIV-1 Nef induces dedifferentiation of podocytes in vivo: a characteristic feature of HIVAN
    Mohammad Husain
    Department of Medicine, Mount Sinai School of Medicine, New York 10029, USA
    AIDS 19:1975-80. 2005
    To determine the specific role of Nef in the pathogenesis of HIV-associated nephropathy.
  47. pmc The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses
    Nathalie Arhel
    Institute of Molecular Virology, University of Ulm, Albert Einstein Allee 11, Ulm, Germany
    J Clin Invest 119:2965-75. 2009
    ..HIV-1 and other primate lentiviruses use their Nef proteins to manipulate the T cell/APC contact zone, the immunological synapse (IS)...
  48. pmc 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)...
  49. doi Human immunodeficiency virus (HIV) type-1, HIV-2 and simian immunodeficiency virus Nef proteins
    Nadine Laguette
    Institut Cochin, CNRS UMR8104, Universite Paris Descartes, Paris, France
    Mol Aspects Med 31:418-33. 2010
    ..Human and simian lentiviruses have acquired non-structural proteins among which Nef plays a major role in the evolution of viral infection towards an immunodeficiency syndrome...
  50. pmc HIV-1 Nef binds a subpopulation of MHC-I throughout its trafficking itinerary and down-regulates MHC-I by perturbing both anterograde and retrograde trafficking
    Ling Yi
    Molecular and Cell Biology Unit, Laboratory of Molecular Immunology, NIAID, Laboratory of Molecular Biophysics, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 285:30884-905. 2010
    The HIV protein Nef is thought to mediate immune evasion and promote viral persistence in part by down-regulating major histocompatibility complex class I protein (MHC-I or HLA-I) from the cell surface...
  51. doi Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T lymphocytes influence viral entry co-receptor expression and susceptibility to superinfection
    Philip Mwimanzi
    Center for AIDS Research, Kumamoto University, Kumamoto, Japan
    Biochem Biophys Res Commun 403:422-7. 2010
    HIV-1 Nef is a key factor for pathogenesis and is known to down-regulate functionally important molecules, including viral entry co-receptor CCR5 and CXCR4, from the surface of HIV-infected cells...
  52. pmc Structure, dynamics, and Hck interaction of full-length HIV-1 Nef
    Jinwon Jung
    Department of Structural Biology and Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA
    Proteins 79:1609-22. 2011
    b>Nef is an HIV accessory protein that plays an important role in the progression of disease after viral infection. It interferes with numerous signaling pathways, one of which involves serine/threonine kinases...
  53. pmc Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways
    Pratima Rawat
    National Centre for Cell Science, Ganeshkhind, Pune 411 007, India
    Nucleic Acids Res 39:5879-92. 2011
    ..We have reported earlier Nef-dependent induction of HSP40 leading to increased HIV-1 gene expression; however, the mechanism of induction ..
  54. pmc HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TNF alpha receptor associated factor 2
    Giorgio Mangino
    Department of Biology, University Roma Tre, Rome, Italy
    PLoS ONE 6:e22982. 2011
    HIV-1 Nef is a virulence factor that plays multiple roles during HIV replication...
  55. pmc The identification of a small molecule compound that reduces HIV-1 Nef-mediated viral infectivity enhancement
    Nopporn Chutiwitoonchai
    Center for AIDS Research, Kumamoto University, Kumamoto, Japan
    PLoS ONE 6:e27696. 2011
    b>Nef is a multifunctional HIV-1 protein that accelerates progression to AIDS, and enhances the infectivity of progeny viruses through a mechanism that is not yet understood...
  56. pmc Immune selection in vitro reveals human immunodeficiency virus type 1 Nef sequence motifs important for its immune evasion function in vivo
    Martha J Lewis
    Department of Medicine, Division of Infectious Diseases, Geffen School of Medicine at UCLA, Los Angeles, California, USA
    J Virol 86:7126-35. 2012
    Human immunodeficiency virus type 1 (HIV-1) Nef downregulates major histocompatibility complex class I (MHC-I), impairing the clearance of infected cells by CD8(+) cytotoxic T lymphocytes (CTLs)...
  57. pmc Epitope targeting and viral inoculum are determinants of Nef-mediated immune evasion of HIV-1 from cytotoxic T lymphocytes
    Diana Y Chen
    Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
    Blood 120:100-11. 2012
    The impact of HIV-1 Nef-mediated HLA-I down-regulation on CD8(+) cytotoxic T lymphocytes (CTLs) varies by epitope, but the determining factors have not been elucidated...
  58. pmc HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation
    Ushani S Rajapaksa
    Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom
    Proc Natl Acad Sci U S A 109:13353-8. 2012
    ..HIV-1 negative regulatory factor (Nef) mediates down-regulation of surface expression of class I HLA (HLA-I) and may therefore impair immune recognition ..
  59. 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...
  60. 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.
  61. 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 ..
  62. 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...
  63. 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 ..
  64. 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...
  65. 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...
  66. 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 ..
  67. 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...
  68. 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...
  69. pmc 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...
  70. pmc 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...
  71. 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...
  72. 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 ..
  73. pmc 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...
  74. pmc 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...
  75. pmc 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...
  76. 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 ..
  77. 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...
  78. pmc 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 ..
  79. pmc 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...
  80. pmc 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...
  81. pmc 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...
  82. 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...
  83. 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 ..
  84. 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...
  85. 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...
  86. pmc 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...
  87. 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...
  88. pmc 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)...
  89. 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...
  90. pmc 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...
  91. pmc 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...
  92. pmc 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...
  93. pmc 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...
  94. 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...
  95. pmc 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...
  96. 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...
  97. pmc 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...
  98. 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 ..
  99. 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...
  100. pmc 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...
  101. pmc 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...

Research Grants17

  1. CARDIAC LESIONS IN HIV1 TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2001
    ..End of Abstract) ..
  2. 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. ..
  3. 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...
  4. 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...
  5. Selective Inhibitors of SRC Family Kinases in Neoplasia
    THOMAS SMITHGALL; Fiscal Year: 2002
    ..Combined with the in vitro assays, we hope to identify novel inhibitory activities that target specific Src kinase isoforms and oncogenic signaling pathways. ..
  6. Src Family Kinases as Molecular Targets for HIV/Nef
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
    The HIV-1 Nef protein is essential for high-titer viral replication and AIDS progression. Nef functions by interacting with multiple host cell signaling proteins, including the members of the Src protein-tyrosine kinase family...
  7. Cytoplasmic Tyrosine Kinase Pathways and ES Cell Fate
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
    ..The ultimate utility of stem cells in clinical medicine depends upon safe and effective methods for manipulating their renewal and differentiation in culture. ..
  8. Targeting HIV-1 Nef with Small Molecules
    THOMAS SMITHGALL; Fiscal Year: 2008
    unreadable] DESCRIPTION (provided by applicant): The HIV-1 accessory protein Nef is essential for high-titer viral replication and AIDS progression...
  9. Pathogenesis of HIVAN: the role of Nef
    JOHN HE; Fiscal Year: 2007
    ..Studies from transgenic mice suggest that Nef, one of the HIV accessory proteins, plays an important role in the pathogenesis of HIVAN...
  10. Src Family Tyrosine Kinases in Tumor Cell Signaling
    THOMAS SMITHGALL; Fiscal Year: 2007
    ..Successful completion of these studies will provide strong validation of myeloid-specific Src kinases as targets for second-generation anti-CML drug development. ..
  11. REGULATION OF P93 C FES TYROSINE KINASE ACTIVITY
    THOMAS SMITHGALL; Fiscal Year: 2005
    ..These studies will help to elucidate the molecular mechanisms that regulate Fes tyrosine kinase activity and to identify the signal transduction pathways utilized by Fes to transmit signals for differentiation. ..
  12. Determine the Transcriptional Activity of Non-integrated HIV-1 DNA
    Yuntao Wu; Fiscal Year: 2008
    ..Additionally, non-integrated viral DNA could serve as clinical markers for disease progression in certain situation. [unreadable] [unreadable] [unreadable]..
  13. Tools for Testing HIV Immune-Control and Vaccine Models
    W David Wick; Fiscal Year: 2009
    ..These theoretical models and experimental protocols should aid in understanding the outcome of a T-cell vaccine trial and in formulating better candidate vaccines. ..
  14. Targeting Brain Macrophages by a novel lentiviral vector
    Yuntao Wu; Fiscal Year: 2006
    ..abstract_text> ..
  15. Role of specific Nef functions in AIDS pathogenesis
    Frank Kirchhoff; Fiscal Year: 2008
    unreadable] DESCRIPTION (provided by applicant): 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 ..
  16. The MHC-I, HIV-1 Nef, AP-1 Complex
    John Guatelli; Fiscal Year: 2008
    ..DESCRIPTION (provided by applicant): 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-..
  17. 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...