nef

Summary

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

Top Publications

  1. 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
  2. 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
  3. pmc HIV-1 Nef: at the crossroads
    John L Foster
    Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Retrovirology 5:84. 2008
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Detail Information

Publications157 found, 100 shown here

  1. 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...
  2. 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 ..
  3. pmc HIV-1 Nef: at the crossroads
    John L Foster
    Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Retrovirology 5:84. 2008
    ..Interest in attenuated vaccines has centered on isolated cases of patients infected with HIV-1 containing a deleted nef gene. Nef is a multifunctional accessory protein that is necessary for full HIV-1 virulence...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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 ..
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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...
  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. 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...
  18. 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...
  19. 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...
  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. 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 ..
  22. 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...
  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. 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)...
  26. 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 ..
  27. 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-..
  28. 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...
  29. 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...
  30. pmc Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef
    Sebastian Breuer
    Abteilung Physikalische Biochemie, Max Planck Institut fur molekulare Physiologie, Dortmund, Germany
    PLoS ONE 6:e20033. 2011
    Increased spread of HIV-1 and rapid emergence of drug resistance warrants development of novel antiviral strategies. Nef, a critical viral pathogenicity factor that interacts with host cell factors but lacks enzymatic activity, is not ..
  31. 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...
  32. 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...
  33. 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 ..
  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 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...
  36. 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...
  37. 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 ..
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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...
  45. 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.
  46. 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)...
  47. ncbi Interaction between Nef and phosphatidylinositol-3-kinase leads to activation of p21-activated kinase and increased production of HIV
    Thomas Linnemann
    Howard Hughes Medical Institute, University of California at San Francisco, 94143, USA
    Virology 294:246-55. 2002
    The negative factor (Nef) is one of six accessory proteins from primate lentiviruses (HIV-1, HIV-2, and SIV). It leads to high levels of viremia and the progression to AIDS in monkeys and humans...
  48. 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...
  49. ncbi The HIV-1 pathogenicity factor Nef interferes with maturation of stimulatory T-lymphocyte contacts by modulation of N-Wasp activity
    Claudia Haller
    Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
    J Biol Chem 281:19618-30. 2006
    The Nef protein is a key determinant of human immunodeficiency virus (HIV) pathogenicity that, among other activities, sensitizes T-lymphocytes for optimal virus production...
  50. pmc HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells
    Malinda R Schaefer
    Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, United States of America
    PLoS Pathog 4:e1000131. 2008
    To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I)...
  51. 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)...
  52. 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...
  53. 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...
  54. 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...
  55. 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...
  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 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...
  58. 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...
  59. 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...
  60. 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 ..
  61. pmc HIV-1 Nef disrupts intracellular trafficking of major histocompatibility complex class I, CD4, CD8, and CD28 by distinct pathways that share common elements
    Jolie A Leonard
    Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA
    J Virol 85:6867-81. 2011
    The Nef protein is an important HIV virulence factor that promotes the degradation of host proteins to augment virus production and facilitate immune evasion...
  62. pmc The Nef-infectivity enigma: mechanisms of enhanced lentiviral infection
    Jolien Vermeire
    Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Belgium
    Curr HIV Res 9:474-89. 2011
    The Nef protein is an essential factor for lentiviral pathogenesis in humans and other simians. Despite a multitude of functions attributed to this protein, the exact role of Nef in disease progression remains unclear...
  63. 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 ..
  64. 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...
  65. 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...
  66. 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...
  67. pmc 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)...
  68. 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 ..
  69. 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...
  70. 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.
  71. 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 ..
  72. 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...
  73. 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...
  74. pmc 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...
  75. 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 ..
  76. 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...
  77. 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...
  78. 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 ..
  79. 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...
  80. 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...
  81. 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...
  82. 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 ..
  83. 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...
  84. 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...
  85. 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...
  86. 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...
  87. 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...
  88. 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...
  89. 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 ..
  90. 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 ..
  91. 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...
  92. pmc 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...
  93. 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...
  94. pmc 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...
  95. 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 ..
  96. pmc 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 ..
  97. 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...
  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. 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...
  100. 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...
  101. pmc 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...

Research Grants73

  1. 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...
  2. CARDIAC LESIONS IN HIV1 TRANSGENIC MICE
    Paul Jolicoeur; Fiscal Year: 2001
    ..End of Abstract) ..
  3. 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. ..
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. Tools for Testing HIV Immune-Control and Vaccine Models
    W Wick; Fiscal Year: 2007
    ..These theoretical models and experimental protocols should aid in understanding the outcome of a T-cell vaccine trial and in formulating better candidate vaccines. ..
  9. Tools for Testing HIV Immune-Control and Vaccine Models
    W David Wick; Fiscal Year: 2005
    ..abstract_text> ..
  10. 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. ..
  11. Targeting Brain Macrophages by a novel lentiviral vector
    Yuntao Wu; Fiscal Year: 2006
    ..abstract_text> ..
  12. Structure Based Themodynamic Studies of HIV-1 Protease
    Ernesto Freire; Fiscal Year: 2010
    ....
  13. 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...
  14. 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. ..
  15. Role of HIPK2 in Kidney Tubulointerstitial Injury
    AVI MA apos AYAN; Fiscal Year: 2010
    ....
  16. 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. ..
  17. 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. ..
  18. 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. ..
  19. 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 ..
  20. 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. ..
  21. 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...
  22. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2004
    ....
  23. 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...
  24. 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...
  25. 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...
  26. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2007
    ..abstract_text> ..
  27. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2005
    ....