nef gene products

Summary

Summary: Products of the HIV nef gene (formerly 3'-orf gene). The products trans-suppress viral replication and function as negative regulators of transcription. nef stands for negative factor.

Top Publications

  1. 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
  2. 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
  3. 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
  4. 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
  5. ncbi HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology
    M Emerman
    Division of Molecular Medicine, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North Mailstop C2 023, Seattle, Washington 98109 1024, USA
    Science 280:1880-4. 1998
  6. 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
  7. pmc Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load
    M M Addo
    Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School Fenway Community Health Center Lemuel Shattuck Hospital, Boston, Massachusetts 02129, USA
    J Virol 77:2081-92. 2003
  8. pmc Disassembly of human immunodeficiency virus type 1 cores in vitro reveals association of Nef with the subviral ribonucleoprotein complex
    Brett M Forshey
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2363, USA
    J Virol 77:4409-14. 2003
  9. ncbi Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA
    Photini Kiepiela
    HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZuluNatal, 719 Umbilo Road, Durban 4015, South Africa
    Nature 432:769-75. 2004
  10. ncbi HIV-1 Nef induces the release of inflammatory factors from human monocyte/macrophages: involvement of Nef endocytotic signals and NF-kappa B activation
    Eleonora Olivetta
    Laboratory of Virology, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    J Immunol 170:1716-27. 2003

Research Grants

Detail Information

Publications217 found, 100 shown here

  1. 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
    ..Thus, CD4 down-regulation and promotion of viral growth are two distinct functions of Nef, and the latter is mediated via SH3 binding...
  2. 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...
  3. 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 Nef-SH3 structure also reveals how high affinity and specificity in the SH3 interaction is achieved by the presentation of the PxxP motif within the context of the folded structure of Nef...
  4. 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
    ..Within this region, a dileucine motif, reminiscent of an endocytosis and lysosomal targeting signal found in the CD3 gamma and delta chains, is crucial for CD4 response to Nef...
  5. ncbi HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology
    M Emerman
    Division of Molecular Medicine, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North Mailstop C2 023, Seattle, Washington 98109 1024, USA
    Science 280:1880-4. 1998
    ..Detailed analysis of the interplay between these viral proteins and normal cellular activities has provided new insights into central questions of virology and host cell biology...
  6. 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
    ..Molecular modeling suggests that these residues are involved in formation of an adjacent binding surface for NAK or another critical component of the NAK/Nef complex...
  7. pmc Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load
    M M Addo
    Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School Fenway Community Health Center Lemuel Shattuck Hospital, Boston, Massachusetts 02129, USA
    J Virol 77:2081-92. 2003
    ....
  8. pmc Disassembly of human immunodeficiency virus type 1 cores in vitro reveals association of Nef with the subviral ribonucleoprotein complex
    Brett M Forshey
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2363, USA
    J Virol 77:4409-14. 2003
    ..They further suggest that virion-associated Nef may facilitate an early step in HIV-1 infection following dissociation of the viral capsid in the target cell...
  9. ncbi Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA
    Photini Kiepiela
    HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZuluNatal, 719 Umbilo Road, Durban 4015, South Africa
    Nature 432:769-75. 2004
    ..The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design...
  10. ncbi HIV-1 Nef induces the release of inflammatory factors from human monocyte/macrophages: involvement of Nef endocytotic signals and NF-kappa B activation
    Eleonora Olivetta
    Laboratory of Virology, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    J Immunol 170:1716-27. 2003
    ..Our data add new hints supporting the idea that the presence of Nef is per se heavily detrimental for monocyte/macrophages and relative cross-talking cell types...
  11. ncbi Intracellular versus cell surface assembly of retroviral pseudotypes is determined by the cellular localization of the viral glycoprotein, its capacity to interact with Gag, and the expression of the Nef protein
    Virginie Sandrin
    INSERM U412, Lyon Ecole Normale Supérieure de Lyon, and IFR128 BioSciences Lyon Gerland, Lyon, F 69007 France
    J Biol Chem 281:528-42. 2006
    ..Finally, the expression of Nef proteins specifically enhanced the incorporation of the retroviral GPs by increasing their localization in late endosomes...
  12. 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
    ..Our findings also reveal an evolutionary difference between HIV-1 and HIV-2/SIV in which the Nef proteins utilize structurally distinct motifs for binding cellular adaptors...
  13. ncbi Comparison of overlapping peptide sets for detection of antiviral CD8 and CD4 T cell responses
    Rika Draenert
    Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
    J Immunol Methods 275:19-29. 2003
    ..We conclude that peptides ranging from 15 to 20 amino acids yield similar results in IFN-gamma-based Elispot and ICS assays, and that all are likely to underestimate the true breadth of responses to a given reference strain of virus...
  14. pmc Human immunodeficiency virus type 1 Nef-induced down-modulation of CD4 is due to rapid internalization and degradation of surface CD4
    S S Rhee
    Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892
    J Virol 68:5156-63. 1994
    ..This implies that HIV-1 Nef protein might play a role in triggering a series of T-cell activation-like events, which contribute to p56lck dissociation and internalization of surface CD4 molecules...
  15. ncbi The HIV-1 Nef protein and phagocyte NADPH oxidase activation
    Frederik Vilhardt
    Biology of Ageing Laboratory, Department of Geriatrics, Geneva University Hospitals, Switzerland
    J Biol Chem 277:42136-43. 2002
    ..Rac activation is not sufficient to stimulate the phagocyte NADPH oxidase; however, it markedly enhances the NADPH oxidase response to other stimuli...
  16. pmc Nef-induced CD4 and major histocompatibility complex class I (MHC-I) down-regulation are governed by distinct determinants: N-terminal alpha helix and proline repeat of Nef selectively regulate MHC-I trafficking
    A Mangasarian
    Department of Genetics and Microbiology, University of Geneva, Geneva, Switzerland
    J Virol 73:1964-73. 1999
    ....
  17. pmc Human immunodeficiency virus type 1 Nef associates with a cellular serine kinase in T lymphocytes
    E T Sawai
    Department of Medicine, University of California, San Francisco 94143 0128
    Proc Natl Acad Sci U S A 91:1539-43. 1994
    ..These findings present evidence that a serine kinase activity is associated with Nef expressed in human T lymphocytes...
  18. pmc Interactions between Nef and AIP1 proliferate multivesicular bodies and facilitate egress of HIV-1
    Luciana J Costa
    Molecular Virology Laboratory, Dep of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Retrovirology 3:33. 2006
    ..In this report, we investigated further the ability of Nef to facilitate the replication of HIV-1...
  19. pmc A hydrophobic binding surface on the human immunodeficiency virus type 1 Nef core is critical for association with p21-activated kinase 2
    Kristin Agopian
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, JFB 816, 44 Binney St, Boston, Massachusetts 02115, USA
    J Virol 80:3050-61. 2006
    ..This binding surface includes exposed and recessed hydrophobic residues and may participate in an as-yet-unidentified protein-protein interaction to facilitate Pak2 activation...
  20. pmc Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02: a paradigm for virus evolution and persistence?
    Thorsten U Vogel
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
    J Virol 76:11623-36. 2002
    ..Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection...
  21. 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
    ..We conclude that Nef assembles a multiprotein signaling complex which is required for the optimal replication of HIV-1...
  22. 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
    ....
  23. 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
    ..Together, our results demonstrate that Nef alters both the amount and composition of signaling microclusters. We propose modulation of actin dynamics as an important mechanism for Nef-induced alterations of TCR signaling...
  24. 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...
  25. pmc Structure--function relationships in HIV-1 Nef
    M Geyer
    Howard Hughes Medical Institute, University of California, San Francisco 94143 0703, CA, USA
    EMBO Rep 2:580-5. 2001
    ..In contrast, the interaction sites for signalling molecules that contain SH3 domains or the p21-activated kinases are associated with the well folded core domain, suggesting the recognition of highly structured protein surfaces...
  26. pmc Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes
    Otto O Yang
    Division of Infectious Diseases and AIDS Institute, UCLA Medical Center, Los Angeles, California 90095, USA
    J Virol 76:1626-31. 2002
    ..We conclude that Nef (and not Vpr) contributes to functional HIV-1 immune evasion and that this effect is mediated by diminished antigen presentation to CTL...
  27. pmc Determinants of increased replicative capacity of serially passaged simian immunodeficiency virus with nef deleted in rhesus monkeys
    Louis Alexander
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
    J Virol 77:6823-35. 2003
    ..These results delineate sequence changes in SIV that can compensate for the loss of the nef gene to partially restore replicative and pathogenic potential in rhesus monkeys...
  28. pmc CD4 down-regulation by nef alleles isolated from human immunodeficiency virus type 1-infected individuals
    R Mariani
    Cold Spring Harbor Laboratory, NY 11724
    Proc Natl Acad Sci U S A 90:5549-53. 1993
    ..Methodology described here provides quantitative assays to establish whether alterations in nef correlate with the dynamics of disease progression in human AIDS...
  29. pmc Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: relationship to viral load in untreated HIV infection
    M R Betts
    Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9113, USA
    J Virol 75:11983-91. 2001
    ..These results suggest that overall frequencies of HIV-specific T cells are not the sole determinant of immune-mediated protection in HIV-infection...
  30. ncbi Role of Nef in primate lentiviral immunopathogenesis
    F Kirchhoff
    Institute of Virology, University of Ulm, 89081 Ulm, Germany
    Cell Mol Life Sci 65:2621-36. 2008
    ..This evolutionary loss of a specific Nef function may contribute to the high virulence of HIV-1 in humans...
  31. ncbi High viral burden in the presence of major HIV-specific CD8(+) T cell expansions: evidence for impaired CTL effector function
    S Kostense
    Department of Clinical Viro Immunology, CLB Sanquin Blood Supply Foundation and Laboratory for Clinical and Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands
    Eur J Immunol 31:677-86. 2001
    ....
  32. pmc The Nef protein of human immunodeficiency virus is a broad-spectrum modulator of chemokine receptor cell surface levels that acts independently of classical motifs for receptor endocytosis and Galphai signaling
    Nico Michel
    Department of Virology, University of Heidelberg, D 69120 Heidelberg, Germany
    Mol Biol Cell 17:3578-90. 2006
    ..Nef uses a mechanism that is distinct from well-established pathways orchestrating CKR metabolism and offers an interesting tool to study the multifaceted biology of CKRs...
  33. pmc Nef binds p6* in GagPol during replication of human immunodeficiency virus type 1
    Luciana J Costa
    Department of Medicine, University of California San Francisco, UCSF Mt Zion Cancer Center, 2340 Sutter Street, San Francisco, CA 94115, USA
    J Virol 78:5311-23. 2004
    ..Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1...
  34. ncbi Nef: agent of cell subversion
    Vivek K Arora
    Department of Internal Medicine, Division of Infectious Diseases Y9 206, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9113, USA
    Microbes Infect 4:189-99. 2002
    ..The mechanisms by which this small protein modulates distinct host cell properties provide intriguing insight into the intricate interaction between virus and host...
  35. pmc Human immunodeficiency virus-1 Nef expression induces intracellular accumulation of multivesicular bodies and major histocompatibility complex class II complexes: potential role of phosphatidylinositol 3-kinase
    Pamela Stumptner-Cuvelette
    Institut National de la Santé et de la Recherche Médicale U520, Institut Curie, Section de recherche 75005 Paris, France
    Mol Biol Cell 14:4857-70. 2003
    ..Given that human immunodeficiency virus recruits the MVB machinery for its assembly process, our data raise the possibility that Nef is involved in viral assembly through its effect on MVBs...
  36. 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
    ....
  37. ncbi The N-terminus of Nef from HIV-1/SIV associates with a protein complex containing Lck and a serine kinase
    A S Baur
    Institut fur Klinische und Molekulare Virologie, Universitat Erlangen Nurnberg, Erlangen, Federal Republic of Germany
    Immunity 6:283-91. 1997
    ..Deletion of a short amphipathic alpha-helix in the N-terminus, which was found to be conserved in all Nef proteins, inhibited association of the NAKC and significantly reduced virion infectivity...
  38. ncbi Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse
    Maria Isabel Thoulouze
    Unite de Biologie Cellulaire des Lymphocytes, Centre National de la Recherche Scientifique Unité de Recherche Associée 1930, Institut Pasteur, 25 28 rue Dr Roux, 75724 Paris Cedex 15, France
    Immunity 24:547-61. 2006
    ..Alteration of endocytic and signaling networks at the immunological synapse likely impacts the function and fate of HIV-1-infected cells...
  39. 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
    ..The likely consequence of the concerted down-regulation of CD28, CD4 and/or CD3 by Nef is disruption of antigen-specific signaling machineries in infected T cells following a productive antigen recognition event...
  40. ncbi The HIV Nef protein alters Ca(2+) signaling in myelomonocytic cells through SH3-mediated protein-protein interactions
    M Foti
    Department of Morphology, Geneva Medical School, University of Geneva, CH 1225 Geneva, Switzerland
    J Biol Chem 274:34765-72. 1999
    ..Collectively, our results demonstrate that the human immunodeficiency virus 1 Nef protein manipulates intracellular Ca(2+) stores through SH3-mediated interactions in myelomonocytic cells...
  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
    ..This observation sheds new light on the biochemical function of Nef and offers new opportunities for the future development of HIV chemotherapy...
  42. 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
    ..We propose that Nef diverts MHC-1 proteins into a PI 3-kinase-dependent transport pathway that prevents expression on the cell surface...
  43. 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
    ..These data provide new insights into the cellular basis of HIV-1 immunoevasion...
  44. 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 biological purpose of this internalization has, however, remained unclear...
  45. pmc Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibility complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking
    Maya Williams
    Graduate Program in Cellular and Molecular Biology, University of Michigan University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    J Virol 76:12173-84. 2002
    ..In addition, they provide the first direct evidence indicating that Nef functions as an adaptor molecule able to link MHC-I to cellular trafficking proteins...
  46. ncbi The HIV-1 nef protein interferes with phosphatidylinositol 3-kinase activation 1
    A Graziani
    Institute for Cancer Research and Treatment IRCC, University of Torino Medical School, 10126 Torino, Italy
    J Biol Chem 271:6590-3. 1996
    ..These data show that Nef affects selectively the PI 3-kinase signaling pathway and suggest that this interference results in some of the HIV adverse effects on host cell functions...
  47. ncbi Interactions between HIV1 Nef and vacuolar ATPase facilitate the internalization of CD4
    X Lu
    Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, 94143 0703, USA
    Immunity 8:647-56. 1998
    ..Direct interactions between Nef and NBP1 were correlated with the ability of Nef to internalize CD4. The expression of the antisense NBP1 abrogated these effects. We conclude that NBP1 helps to connect Nef with the endocytic pathway...
  48. pmc Human immunodeficiency virus type 1 Nef protein inhibits activation pathways in peripheral blood mononuclear cells and T-cell lines
    A Greenway
    AIDS Cellular Biology Unit, National Centre in HIV Virology Research, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia
    J Virol 69:1842-50. 1995
    ..Also, proliferation and posttranslational modification of p56lck in response to IL-2 stimulation were not profoundly affected by treatment of PBMC with Nef25 compared with Nef27.(ABSTRACT TRUNCATED AT 400 WORDS)..
  49. ncbi Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV-1(SF2) Nef
    Simone I Giese
    Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
    Virology 355:175-91. 2006
    ....
  50. pmc HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail
    Jeremiah F Roeth
    Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA
    J Cell Biol 167:903-13. 2004
    ..In sum, our evidence suggests that binding of AP-1 to the Nef-MHC-I complex is an important step required for inhibition of antigen presentation by HIV...
  51. 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
    ..Based on recent structural analysis, our results suggest that the di-leucine-binding domain consists of a HEAT or ARM repeat protein fold...
  52. 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
    ..In contrast, Jurkat cells with the threonine variant of Nef are at least partially restored in their ability to recruit NF-kB and AP-1...
  53. 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
    ..Altogether, these results demonstrate that there is an overlapping, but noncompetitive, sequence requirement in the cytoplasmic domain of CD4 for lck association and down-regulation by Nef...
  54. pmc Antiviral effects of human immunodeficiency virus type 1-specific small interfering RNAs against targets conserved in select neurotropic viral strains
    Rajnish S Dave
    Dorrance H Hamilton Laboratories, Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University, 1020 Locust St, Suite 329, Philadelphia, PA 19107, USA
    J Virol 78:13687-96. 2004
    ....
  55. ncbi Impacts of avidity and specificity on the antiviral efficiency of HIV-1-specific CTL
    Otto O Yang
    Division of Infectious Diseases and AIDS Institute, University of California, Los Angeles Medical Center, Los Angeles, CA 90095, USA
    J Immunol 171:3718-24. 2003
    ..These results suggest that CTL specificity may have a pivotal role in the immunopathogenesis of infection, and that simple quantitative measures of CTL may be insufficient indicators of the CTL response to HIV-1...
  56. ncbi Detection of high frequencies of HIV-1 cross-subtype reactive CD8 T lymphocytes in the peripheral blood of HIV-1-infected Kenyans
    Jeffrey R Currier
    US Military HIV Research Program, Suite 200, 13 Taft Court, Rockville, MD 20850, USA
    AIDS 17:2149-57. 2003
    ..To quantitate rapidly the frequency of HIV-1 subtype-specific and broadly HIV-1 cross-subtype-reactive CD8 T cells in the peripheral blood of HIV-1-infected individuals from a geographical region of multiple subtype endemicity...
  57. 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
    ..Our data demonstrate that Nef has at least two independent mechanisms to alter TCR function and thus may interfere with a range of T cell responses...
  58. 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
    ..This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans...
  59. pmc Human immunodeficiency virus type 1 Nef binds to tumor suppressor p53 and protects cells against p53-mediated apoptosis
    Alison L Greenway
    AIDS Cellular Biology Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria 3078, Australia
    J Virol 76:2692-702. 2002
    ..These data show that HIV-1 Nef may augment HIV replication by prolonging the viability of infected cells by blocking p53-mediated apoptosis...
  60. ncbi Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA
    Y Wu
    Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892-4034, USA
    Science 293:1503-6. 2001
    ..Here, we report that HIV infection leads to selective transcription of the nef and tat genes before integration. This preintegration transcription in quiescent cells leads to increased T cell activation and viral replication...
  61. pmc The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes
    M E Greenberg
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    EMBO J 17:2777-89. 1998
    ....
  62. 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
    ..Thus, Nef also transports newly synthesized cholesterol to the site of viral budding. As such, it provides essential building blocks for the formation of viruses that replicate optimally in the host...
  63. pmc Human immunodeficiency virus type 1 Nef: adapting to intracellular trafficking pathways
    Jeremiah F Roeth
    Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA
    Microbiol Mol Biol Rev 70:548-63. 2006
    ....
  64. ncbi Cell-surface expression of CD4 reduces HIV-1 infectivity by blocking Env incorporation in a Nef- and Vpu-inhibitable manner
    J Lama
    La Jolla Institute for Allergy and Immunology Molecular Immunology Division, 10355 Science Center Drive, San Diego, California 92121, USA
    Curr Biol 9:622-31. 1999
    ..Such functional convergence strongly suggests that CD4 downregulation is critical for optimal viral replication, yet the significance of this phenomenon has so far remained a puzzle...
  65. 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
    ..These results will facilitate both the elucidation of the role of Nef in pathogenesis and the development of specific inhibitors of this highly conserved function of Nef...
  66. 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 data also suggest that an influence on the distribution of cellular transmembrane proteins may mechanistically unite two previously distinct properties of Nef: down-regulation of CD4 and enhancement of viral infectivity...
  67. pmc Modulation of cellular protein trafficking by human immunodeficiency virus type 1 Nef: role of the acidic residue in the ExxxLL motif
    Scott H Coleman
    University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
    J Virol 80:1837-49. 2006
    ..The data suggest that the E160 residue plays a differential role in the modulation of leucine-dependent Nef-targets and support a model in which distinct AP complexes are used by Nef to modulate different cellular proteins...
  68. pmc HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes
    V Piguet
    Department of Genetics and Microbiology, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland
    Nat Cell Biol 2:163-7. 2000
    ..These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway...
  69. 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
    ..These results demonstrate that CD4 downregulation by Nef plays a crucial role in HIV-1 replication in activated T cells and underscore the potential for the development of therapies targeting this conserved activity of Nef...
  70. pmc Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition
    Atze T Das
    Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Virol 78:2601-5. 2004
    ..However, as is known for antiviral drug therapy against HIV-1, antiviral approaches involving RNAi should be used in a combined fashion to prevent the emergence of resistant viruses...
  71. ncbi Interactions of HIV-1 nef with the mu subunits of adaptor protein complexes 1, 2, and 3: role of the dileucine-based sorting motif
    H M Craig
    Department of Pathology and, Department of Medicine, San Diego Veterans Affairs Medical Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, California, 92093 0679, USA
    Virology 271:9-17. 2000
    ....
  72. 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
    ..The stimulation of MHC-I endocytosis by Nef represents a previously undocumented viral mechanism for evading the immune response...
  73. pmc Comprehensive screening for human immunodeficiency virus type 1 subtype-specific CD8 cytotoxic T lymphocytes and definition of degenerate epitopes restricted by HLA-A0207 and -C(W)0304 alleles
    Jeffrey R Currier
    U S Military HIV Research Program, Rockville, Maryland 20850, USA
    J Virol 76:4971-86. 2002
    ..These findings provide biological validation of HLA supertypes in HIV-1 CTL recognition and support earlier studies of cross-subtype CTL responses during HIV-1 infection...
  74. ncbi Replicating Ad-recombinants encoding non-myristoylated rather than wild-type HIV Nef elicit enhanced cellular immunity
    Bo Peng
    Vaccine Branch, Center for Cancer Research, National Cancer Institute, 41 Medlars Drive, Bethesda, MD 20892, USA
    AIDS 20:2149-57. 2006
    ..To determine if immunization with non-myristoylated nef would elicit enhanced cellular immune responses resulting from improved presentation of Nef peptides by MHC-I on the cell surface, and enhanced T-cell help...
  75. 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
    ..Cotransfection of an activated protein kinase C-theta (PKC-theta) with Nef implicated PKC-theta as a possible physiological cofactor of Nef in promoting NFAT-dependent gene expression and T-cell activation...
  76. pmc Nef-mediated disruption of HLA-A2 transport to the cell surface in T cells
    Matthew R Kasper
    Department of Microbiology and Immunology, The University of Michigan, Ann Arbor, Michigan 48109, USA
    J Virol 77:3041-9. 2003
    ....
  77. ncbi HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion
    Marielle Cavrois
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141 9100, United States
    Virology 328:36-44. 2004
    ....
  78. pmc Differential proteasomal processing of hydrophobic and hydrophilic protein regions: contribution to cytotoxic T lymphocyte epitope clustering in HIV-1-Nef
    Maria Lucchiari-Hartz
    Department of Cellular Immunology, Max Planck Institute of Immunobiology, Stubeweg 51, D 79108 Freiburg, Germany
    Proc Natl Acad Sci U S A 100:7755-60. 2003
    ..The results suggest that differential proteasomal processing contributes importantly to the clustering of CTL epitopes in hydrophobic regions...
  79. pmc The membrane-proximal tyrosine-based sorting signal of human immunodeficiency virus type 1 gp41 is required for optimal viral infectivity
    John R Day
    Division of Biological Sciences, University of California, San Diego, USA
    J Virol 78:1069-79. 2004
    ....
  80. ncbi Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machinery
    Matthias Geyer
    Department of Medicine, University of California, San Francisco, California 94143 0703, USA
    J Biol Chem 277:28521-9. 2002
    ..Finally, blocking the expression of V1H decreased the enhancement of virion infectivity by Nef. Thus, V1H can function as an adaptor for interactions between Nef and AP-2...
  81. 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
    ..Nef interacts with the medium (mu) subunit of AP adaptor complexes involved in the recognition of tyrosine-based sorting signals, likely facilitating the connection between MHC I and the clathrin-dependent sorting machinery...
  82. ncbi Domain assembly, surface accessibility and sequence conservation in full length HIV-1 Nef
    M Geyer
    Howard Hughes Medical Institute, University of California, San Francisco, CA 94143 0703, USA
    FEBS Lett 496:91-5. 2001
    ..The high amount of flexible regions in Nef accounts for the large surface and the multiple interaction sites the protein exhibits...
  83. 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
    ..These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication...
  84. 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
    ..Thus, the interaction between Nef and Vav initiates a signaling cascade that changes structural and physiological parameters in the infected cell...
  85. pmc PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic
    C M Crump
    Vollum Institute, L 474, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201 3098, USA
    EMBO J 20:2191-201. 2001
    ..These studies demonstrate the requirement for PACS-1 interactions with adaptor proteins in multiple processes, including secretory granule biogenesis and HIV-1 pathogenesis...
  86. 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
    ..Our report suggests that functionally and conformationally distinct Nef isoforms modulate HIV replication on the interaction level with the TCR-signaling environment once the virus enters the T cell compartment...
  87. pmc Nef from human immunodeficiency virus type 1(F12) inhibits viral production and infectivity
    O T Fackler
    Department of Medicine, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94143-0703, USA
    J Virol 75:6601-8. 2001
    ..The identification of a dominant-negative protein for the production and infectivity of HIV suggests that Nef plays an active role at this stage of the viral replicative cycle...
  88. ncbi Impact of antigen expression kinetics on the effectiveness of HIV-specific cytotoxic T lymphocytes
    Carel A van Baalen
    Institute of Virology, Erasmus MC Rotterdam, The Netherlands
    Eur J Immunol 32:2644-52. 2002
    ..This provides rationale for immunization strategies that aim at inducing, boosting or skewing CTL responses to early regulatory proteins in AIDS vaccine development...
  89. 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
    ..Thus, the dileucine motif in HIV-1 is required for CD4 downregulation and for interaction with clathrin adaptor complexes...
  90. pmc Refined solution structure and backbone dynamics of HIV-1 Nef
    S Grzesiek
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0520, USA
    Protein Sci 6:1248-63. 1997
    ..A refined structure has been determined based on additional constraints for side-chain and backbone dihedral angles derived from a large number of three-bond J-coupling and ROE data...
  91. 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
    ..New genes associated with Nef include CDK9, the induction of which enhances Tat function. Thus, Nef acts as a master switch early in the viral life cycle, forcing an environment conducive to dynamic viral production...
  92. pmc Human immunodeficiency virus type 1 Nef protein down-regulates transcription factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor stimulation
    J C Bandres
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110
    J Virol 68:3243-9. 1994
    ....
  93. ncbi Modulation of the immunological synapse: a key to HIV-1 pathogenesis?
    Oliver T Fackler
    Oliver T Fackler is at the Department of Virology, University of Heidelberg, D 69120 Heidelberg, Germany
    Nat Rev Immunol 7:310-7. 2007
    ..We propose that modulating lymphocyte signalling, apoptosis and intracellular trafficking ensures efficient spread of the virus in the hostile environment of the immune system...
  94. 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
    ..Cooperation between those mechanisms may enable Nef to efficiently inhibit MHC II function...
  95. 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
    ..Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism...
  96. pmc Distinct trafficking pathways mediate Nef-induced and clathrin-dependent major histocompatibility complex class I down-regulation
    S Le Gall
    Unité Rétrovirus et Transfert Génétique, URA CNRS 1930, France
    J Virol 74:9256-66. 2000
    ..Moreover, trafficking of A2-endo was still affected by the viral protein, indicating additive effects of prototypic signals and Nef. Therefore, distinct trafficking pathways regulate clathrin-dependent and Nef-induced MHC-I modulation...
  97. pmc Recognition of dileucine-based sorting signals from HIV-1 Nef and LIMP-II by the AP-1 gamma-sigma1 and AP-3 delta-sigma3 hemicomplexes
    Katy Janvier
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 163:1281-90. 2003
    ..These observations reveal a novel mode of recognition of sorting signals involving the gamma/delta and sigma subunits of AP-1 and AP-3...
  98. ncbi Human immunodeficiency virus (HIV)-1 proteins and cytoskeleton: partners in viral life and host cell death
    P Matarrese
    Section of Cell Aging and Degeneration, Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Viale Regina Elena 299, Rome, Italy
    Cell Death Differ 12:932-41. 2005
    ..The microfilament system seems thus to be a sort of cytoplasmic supervisor of the viral particle, the host cell and the bystander cell's very fate...
  99. pmc Human immunodeficiency virus-specific responses in adult Ugandans: patterns of cross-clade recognition
    Banson Barugahare
    Joint Clinical Research Centre, Kampala, Uganda
    J Virol 79:4132-9. 2005
    ..High sequence homologies were also observed between consensus peptides and sequences from viral isolates, supporting the use of consensus amino acid sequences to identify immunogenic regions in studies of large populations...
  100. ncbi The Pro78 residue regulates the capacity of the human immunodeficiency virus type 1 Nef protein to inhibit recycling of major histocompatibility complex class I molecules in an SH3-independent manner
    Nicoletta Casartelli
    Division of Immunology and Infectious Disease, Children s Hospital Bambino Gesu, Piazza S Onofrio 4, 00165 Rome, Italy
    J Gen Virol 87:2291-6. 2006
    ..In addition, it is demonstrated that P72 and P75, and thus the SH3-binding capacity, are fully dispensable for Nef activity on MHC-I...
  101. ncbi HIV-1 Nef disrupts antigen presentation early in the secretory pathway
    Matthew R Kasper
    Department of Microbiology, The University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 280:12840-8. 2005
    ..MHC-I complex. We propose that the assembly of a Nef.MHC-I.adaptor protein 1 complex early in the secretory pathway is important for Nef activity...

Research Grants35

  1. PATHOGENESIS OF HIV IN CD4 CELLS
    James Hoxie; Fiscal Year: 1993
    ..Immunoprecipitation and Western blot assays will be utilized to quantitate NEF gene products and to identify both myristylated and phosphorylated forms of this protein in infected cells...
  2. CONSEQUENCES OF NEF EXPRESSION ON CNS PATHOLOGY
    Nora Sarvetnick; Fiscal Year: 2005
    ..These studies will illuminate the mechanism whereby NEF, present in myelmonocytic cells contributes to central nervous system dysfunction associated with HIV infection. ..
  3. HIV REPORTER CELL LINE FOR SCREENING ANTI-SENSE AGENTS
    Howard Gamper; Fiscal Year: 1991
    ..indicator of viral gag, pol, and env regions subject to normal regulation by the viral coded tat, rev, and nef gene products. The H9 cell line will be transfected with this construct and the transient expression of SPAP, p24, and ..
  4. MOLECULAR VIROLOGIC ANALYSIS OF THE NEF GENE OF HIV
    Sunyoung Kim; Fiscal Year: 1992
    ..This proposal is an attempt to investigate more fully the molecular and biochemical properties of nef and also to explore its possible in vivo function(s)...
  5. Mucosal and Peripheral NK-T Cells in HIV Infection
    Otto Yang; Fiscal Year: 2007
    ..Exploring NK-T cells in HIV-1 infection could there have a high impact on the development of new strategies in prevention and treatment. [unreadable] [unreadable]..
  6. CELLULAR FACTORS REQUIRED FOR HIV ENTRY
    Dan Littman; Fiscal Year: 2007
    ..The results of these studies should provide insight into[unreadable] the complex mechanism of HIV entry and may suggest novel approaches for[unreadable] interfering with the earliest step in the HIV life cycle.[unreadable]..
  7. Toxin Gene Deleted C. perfringens as an Oral Delivery Vector
    Yue Chen; Fiscal Year: 2007
    ..Successful completion of this study will create a safe, low-cost and efficient oral delivery vector for vaccine and therapeutic agents. [unreadable] [unreadable]..
  8. Raft/Caveolar Mechanisms in Pulmonary Hypertension
    PRAVIN SEHGAL; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  9. HIV-1 and Host Cell Changes in Disease Progression
    James Mullins; Fiscal Year: 2007
    ..Data will be correlated with markers of disease progression, and correlates will be assessed for their ability to predict the critical events leading to disease, by targeted analysis of additional subjects. ..
  10. Pathogenesis of HIVAN: the role of Nef
    JOHN HE; Fiscal Year: 2007
    ..These studies should elucidate essential mechanism responsible for the development of HIV-associated nephropathy and how Nef plays a role in this pathologic process. ..
  11. CD4 Immune Reconstitution in SIV Infection
    Francois Villinger; Fiscal Year: 2007
    ..Results of these studies will form the basis for future immune reconstitution strategies in human HIV infected patients. ..
  12. IMMUNOREGULATION IN AIDS
    Norman Letvin; Fiscal Year: 2008
    ..3. Nondominant SHIV epitope-specific CTL populations. A. Breadth and magnitude. B. Functional repertoire. C. TCR repertoire. 4. Nondominant epitope-specific CTL and control of SIV replication. [unreadable] [unreadable]..
  13. A New DNA Vaccine Against HIV Disease in Macaques
    Edward Stephens; Fiscal Year: 2008
    ..Vaccine boosts will continue after drug therapy had been withdrawn. These studies will be applicable to HIV infected persons under HAART. ..
  14. MURINE MODEL SYSTEM FOR HIV PATHOGENESIS
    Dan Littman; Fiscal Year: 2008
    ..RNA interference and gene targeting will be used to reduce expression of the mouse enzyme, and we will engineer HIV with Vif that can bind to and induce degradation of mouse apobec3g. [unreadable] [unreadable]..
  15. The MHC-I, HIV-1 Nef, AP-1 Complex
    John Guatelli; Fiscal Year: 2008
    ..By understanding the molecular basis of this linkage, new approaches to drug design may become apparent. [unreadable] [unreadable] [unreadable]..
  16. Screen for Small Molecule Compounds that Modulate the Transcriptional Activity of
    Dan Littman; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  17. Statistical Methods in HIV Vaccine Efficacy Trials
    Peter Gilbert; Fiscal Year: 2009
    ..By improving the design and analysis of efficacy and NHP trials for addressing these areas, the project will benefit public health. ..
  18. INTERACTIONS BETWEEN CMV AND SIV IN RHESUS MACAQUES
    Amitinder Kaur; Fiscal Year: 2007
    ..Specific Aim #3: To examine mechanisms of restoration of CMV-specific immunity in SIV-infected macaques treated with HAART. ..
  19. The T cell response to rapidly evolving HIV antigens
    Daniel Kavanagh; Fiscal Year: 2006
    ..This method will be used to compare the T cell responses to autologous and consensus antigens in chronic HIV infection. ..
  20. Role of Targeted Mutations in ViF on SHIV Pathogenesis
    Edward Stephens; Fiscal Year: 2006
    ..The proposed studies will provide new information on the role of this Vif motif in pathogenesis using a relevant macaque model. ..
  21. COALESCENT METHODS FOR MEASURABLY EVOLVING POPULATIONS
    James Mullins; Fiscal Year: 2001
    ..Develop a coalescent-likelihood method which uses serial samples to estimate piecewise exponential changes in effective population size. ..
  22. Acquisition of High Speed Cell Sorter
    Dan Littman; Fiscal Year: 2002
    ..We believe that the availability of this powerful machine on our campus will elicit new exciting research projects from a variety of scientists working in the fields of cancer, immunology, and animal development. ..
  23. ANTIVIRAL THERAPY AND COMPARTMENTS OF HIV IN VIVO
    James Mullins; Fiscal Year: 2002
    ....
  24. CELLULAR PHYSIOLOGY OF STAT3
    PRAVIN SEHGAL; Fiscal Year: 2002
    ..Establishing the basic subunit structure of the cytosolic 200-400 kDa and 1-2 MDa STAT3-containing complexes in IL-6-free and IL-6-treated cells is a sine qua non for further progress in this field. ..
  25. SHIV ASSOCIATED ENCEPHALOPATHY
    Edward Stephens; Fiscal Year: 2003
    ..It is anticipated that the proposed studies will provide valuable information which will improve our understanding of HIV-1 neuropathogenesis. ..
  26. PATHOGENIC CONVERSION OF ATTENUATED SIV VACCINES
    Earl Sawai; Fiscal Year: 2003
    ..Accordingly, the proposed studies will provide critical insight into molecular changes in the viral genome that are necessary for pathogenic conversion of live-attenuated viral vaccines. ..
  27. OCCURRENCE AND OUTCOME OF DUAL HIV-1 INFECTION
    James Mullins; Fiscal Year: 2004
    ....
  28. Conference HIV Vaccine Development Progress & Prospects
    Norman Letvin; Fiscal Year: 2004
    ..abstract_text> ..
  29. Cell immune responses in SIV-infected sooty mangabeys
    Amitinder Kaur; Fiscal Year: 2004
    ..abstract_text> ..
  30. Effect of Alcohol on SHIV Neuroinvasion
    Edward Stephens; Fiscal Year: 2004
    ..The results of these studies should provide direct evidence on the effect of ethanol on primate lentivirus neuroinvasion and neuropathogenesis. ..
  31. Discovery of biomarkers of pulmonary hypertension
    Rubin Tuder; Fiscal Year: 2005
    ..abstract_text> ..
  32. HIV Infection of Non-Dividing Cells
    Michael Emerman; Fiscal Year: 2010
    ..The identification of the precise viral determinants that allow it access to non-dividing cells may present new drug targets against HIV. ..
  33. Role of specific Nef functions in AIDS pathogenesis
    Frank Kirchhoff; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  34. Accessory roles of Tat in HIV-1 replication
    Michael Emerman; Fiscal Year: 2005
    ..Thus, the overall goal of this proposal is to identify functions attributable to the second exon of Tat and to ascertain the role of these Tat functions in HIV-1 replication and pathogenesis. ..
  35. DNA VACCINE IMMUNITY TO HIV1 AND SIV
    Norman Letvin; Fiscal Year: 2002
    ..This aim therefore studies cross reactivity to a single epitope not multi epitopes. ..