hiv envelope protein gp41

Summary

Summary: Transmembrane envelope protein of the HUMAN IMMUNODEFICIENCY VIRUS which is encoded by the HIV env gene. It has a molecular weight of 41,000 and is glycosylated. The N-terminal part of gp41 is thought to be involved in CELL FUSION with the CD4 ANTIGENS of T4 LYMPHOCYTES, leading to syncytial formation. Gp41 is one of the most common HIV antigens detected by IMMUNOBLOTTING.

Top Publications

  1. pmc Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target
    Laura M Walker
    Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA
    Science 326:285-9. 2009
  2. ncbi Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
    P D Kwong
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA
    Nature 393:648-59. 1998
  3. ncbi Antibody neutralization and escape by HIV-1
    Xiping Wei
    Howard Hughes Medical Institute, University of Alabama at Birmingham, 720 South 20th Street, Kaul 816, Birmingham, Alabama 35294 0024, USA
    Nature 422:307-12. 2003
  4. pmc Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy
    Xiping Wei
    Howard Hughes Medical Institute, Department of Medicine, University of Alabama at Birmingham, 35294, USA
    Antimicrob Agents Chemother 46:1896-905. 2002
  5. ncbi Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
    Johannes F Scheid
    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA
    Nature 458:636-40. 2009
  6. pmc Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer
    Youdong Mao
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 19:893-9. 2012
  7. pmc Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia
    Georgia D Tomaras
    Duke Human Vaccine Institute, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    J Virol 82:12449-63. 2008
  8. pmc Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies
    James M Binley
    IMM2, Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    J Virol 78:13232-52. 2004
  9. pmc Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals
    Yuxing Li
    Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892 3005, USA
    J Virol 83:1045-59. 2009
  10. ncbi Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
    Jinghe Huang
    HIV Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 491:406-12. 2012

Detail Information

Publications248 found, 100 shown here

  1. pmc Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target
    Laura M Walker
    Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA
    Science 326:285-9. 2009
    ..The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses...
  2. ncbi Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
    P D Kwong
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA
    Nature 393:648-59. 1998
    ..Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene...
  3. ncbi Antibody neutralization and escape by HIV-1
    Xiping Wei
    Howard Hughes Medical Institute, University of Alabama at Birmingham, 720 South 20th Street, Kaul 816, Birmingham, Alabama 35294 0024, USA
    Nature 422:307-12. 2003
    ..The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire...
  4. pmc Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy
    Xiping Wei
    Howard Hughes Medical Institute, Department of Medicine, University of Alabama at Birmingham, 35294, USA
    Antimicrob Agents Chemother 46:1896-905. 2002
    ..These findings provide the first evidence for the rapid emergence of clinical resistance to a novel class of HIV-1 entry inhibitors and may be relevant to future treatment strategies involving these agents...
  5. ncbi Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
    Johannes F Scheid
    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA
    Nature 458:636-40. 2009
    ..Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120...
  6. pmc Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer
    Youdong Mao
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 19:893-9. 2012
    ..The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host...
  7. pmc Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia
    Georgia D Tomaras
    Duke Human Vaccine Institute, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    J Virol 82:12449-63. 2008
    ..These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection...
  8. pmc Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies
    James M Binley
    IMM2, Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    J Virol 78:13232-52. 2004
    ..As well as the significance for vaccine design, our data have implications for passive-immunization studies in countries where clade C viruses are common, given that only MAbs b12 and 4E10 were effective against viruses from this clade...
  9. pmc Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals
    Yuxing Li
    Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892 3005, USA
    J Virol 83:1045-59. 2009
    ..These data allow a more detailed understanding of the humoral responses to the HIV-1 Env protein and provide insights regarding the most relevant targets for HIV-1 vaccine design...
  10. ncbi Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
    Jinghe Huang
    HIV Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 491:406-12. 2012
    ..The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein...
  11. pmc Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility
    Marie Pancera
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 107:1166-71. 2010
    ..A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions...
  12. ncbi Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies
    Barton F Haynes
    Duke University School of Medicine, Durham, NC 27710, USA
    Science 308:1906-8. 2005
    ..These results may have important implications for generating effective neutralizing antibody responses by using HIV-1 vaccines...
  13. pmc MPER-specific antibodies induce gp120 shedding and irreversibly neutralize HIV-1
    Claudia R Ruprecht
    Institute of Medical Virology, University Hospital Zurich, Switzerland
    J Exp Med 208:439-54. 2011
    ....
  14. pmc Structure-guided alterations of the gp41-directed HIV-1 broadly neutralizing antibody 2F5 reveal new properties regarding its neutralizing function
    Javier Guenaga
    IAVI Neutralizing Antibody Center at The Scripps Research Institute, La Jolla, California, United States of America
    PLoS Pathog 8:e1002806. 2012
    ..The data suggest a new mechanism of action, important for vaccine design, in which the 2F5 CDRH3 contacts and destabilizes the MPER helix downstream of its core epitope to allow induction of the extended-loop conformation...
  15. pmc HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes
    Kosuke Miyauchi
    Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Cell 137:433-44. 2009
    ..These findings imply that HIV-1 infects cells via endocytosis and envelope glycoprotein- and dynamin-dependent fusion with intracellular compartments...
  16. pmc A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41
    Melody R Davis
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232 2363, USA
    J Virol 80:2405-17. 2006
    ..Our results suggest that an altered interaction between the MA domain of Gag and the gp41 cytoplasmic tail leads to dissociation of gp120 from gp41 during HIV-1 particle assembly, thus resulting in impaired fusion and infectivity...
  17. ncbi Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges
    Morgane Bomsel
    Mucosal Entry of HIV 1 and Mucosal Immunity, Cell Biology and Host Pathogen Interactions Department, Cochin Institute, CNRS UMR 8104, 22 rue Mechain, Paris, France
    Immunity 34:269-80. 2011
    ..The protection observed challenges the paradigm whereby circulating antiviral antibodies are required for protection against HIV-1 infection and may serve in designing a human vaccine against HIV-1-AIDS...
  18. pmc Topology of the C-terminal tail of HIV-1 gp41: differential exposure of the Kennedy epitope on cell and viral membranes
    Jonathan D Steckbeck
    Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 5:e15261. 2010
    ..These data indicate apparently distinct CTT topologies for virion- and cell-associated Env species and add to the case for a reconsideration of CTT topology that is more complex than currently envisioned...
  19. pmc Elicitation of structure-specific antibodies by epitope scaffolds
    Gilad Ofek
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 107:17880-7. 2010
    ..Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation...
  20. pmc Role of HIV membrane in neutralization by two broadly neutralizing antibodies
    S Munir Alam
    Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 106:20234-9. 2009
    ..These results bear directly on strategies for rational design of HIV-1 envelope immunogens...
  21. pmc Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1
    Penny L Moore
    Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA
    J Virol 80:2515-28. 2006
    ..We hypothesize that these nonfunctional forms of Env on particle surfaces serve to divert the antibody response, helping the virus to evade neutralization...
  22. pmc Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope
    Gilad Ofek
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Instiutes of Health, Bethesda, MD 20892, USA
    J Virol 78:10724-37. 2004
    ..Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed...
  23. ncbi Entry inhibitors in the treatment of HIV-1 infection
    John C Tilton
    Department of Microbiology, University of Pennsylvania, 301C Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, United States
    Antiviral Res 85:91-100. 2010
    ..This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010...
  24. pmc Depletion of latent HIV-1 infection in vivo: a proof-of-concept study
    Ginger Lehrman
    University of Texas Southwestern Medical Center at Dallas, Department of Medicine, Division of Infectious Diseases, 5323 Harry Hines Boulevard, Dallas, TX 753901, USA
    Lancet 366:549-55. 2005
    ..Since the chromatin remodeling enzyme histone deacetylase 1 (HDAC1) maintains latency of integrated HIV, we tested the ability of the HDAC inhibitor valproic acid to deplete persistent, latent infection in resting CD4+ T cells...
  25. ncbi HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane
    Zhen Yu J Sun
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Immunity 28:52-63. 2008
    ....
  26. pmc Enhanced HIV-1 neutralization by antibody heteroligation
    Hugo Mouquet
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 109:875-80. 2012
    ..Heterotypic bivalent binding enhanced neutralization compared with the parental antibodies. We conclude that antibody recognition and viral neutralization of HIV can be improved by heteroligation...
  27. ncbi Interaction of endocytic signals from the HIV-1 envelope glycoprotein complex with members of the adaptor medium chain family
    H Ohno
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Virology 238:305-15. 1997
    ..These observations suggest that HIV-1 Env utilizes the protein sorting machinery of the host cells for internalization and sorting at various steps of the endocytic and biosynthetic pathways...
  28. pmc Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin
    Xinzhen Yang
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Virol 76:4634-42. 2002
    ..The melting temperatures and ligand recognition properties of the GCN4- and fibritin-stabilized soluble gp140 glycoproteins suggest that these molecules assume conformations distinct from that of the fusion-active, six-helix bundle...
  29. ncbi Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41
    Rosa M F Cardoso
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Immunity 22:163-73. 2005
    ..These structural insights should assist in the design of immunogens to elicit 4E10-like neutralizing responses...
  30. pmc Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding
    Q J Sattentau
    Academic Department of Genito Urinary Medicine, University College and Middlesex School of Medicine, London, United Kingdom
    J Exp Med 174:407-15. 1991
    ..We propose that these events occurring after CD4 binding are integral components of the membrane fusion reaction between HIV or HIV-infected cells and CD4+ cells...
  31. pmc Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state
    Hillel Haim
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA, USA
    PLoS Pathog 5:e1000360. 2009
    ..This novel strategy for inhibition may be generally applicable to high-potential-energy viral entry machines that are normally activated by receptor binding...
  32. pmc Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L
    Ann J Hessell
    Department of Immunology and Microbial Science and the International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    J Virol 84:1302-13. 2010
    ..The study confirms the protective potential of 2F5 and 4E10 and supports emphasis on HIV immunogen design based on the MPER region of gp41...
  33. pmc Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting
    Lynn Morris
    Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, North Carolina, United States of America
    PLoS ONE 6:e23532. 2011
    ..These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection...
  34. pmc Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated
    Hua Xin Liao
    Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
    J Exp Med 208:2237-49. 2011
    ..These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens...
  35. pmc Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions
    Victor Buzon
    Unit of Virus Host Cell Interactions UMI 3265, Université Joseph Fourier EMBL CNRS, Grenoble, France
    PLoS Pathog 6:e1000880. 2010
    ....
  36. pmc Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions
    Andres Finzi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 37:656-67. 2010
    ..Thus, despite lack of contact with CD4, the gp120 inner-domain layers govern CD4 triggering by participating in conformational transitions within gp120 and regulating the interaction with gp41...
  37. pmc The cytoplasmic domain of the HIV-1 glycoprotein gp41 induces NF-κB activation through TGF-β-activated kinase 1
    Thomas S Postler
    New England Primate Research Center, Department of Microbiology and Molecular Genetics, Harvard Medical School, Southborough, MA 01772 9102, USA
    Cell Host Microbe 11:181-93. 2012
    ..These findings demonstrate an evolutionarily conserved role for gp41CD in activating NF-κB to promote infection...
  38. pmc Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus
    John J Dwyer
    Trimeris Inc, 3500 Paramount Parkway, Morrisville, NC 27560, USA
    Proc Natl Acad Sci U S A 104:12772-7. 2007
    ..The potent antiviral activity against resistant viruses, the difficulty in generating resistant virus, and the extended half-life in vivo make this class of fusion inhibitor peptide attractive for further development...
  39. pmc N-substituted pyrrole derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere with the gp41 six-helix bundle formation and block virus fusion
    Shibo Jiang
    Lindsley F Kimball Research Institute, New York Blood Center, 310 E 67th St, New York, NY 10021, USA
    Antimicrob Agents Chemother 48:4349-59. 2004
    ..Therefore, NB-2 and NB-64 can be used as lead compounds toward designing and developing more potent small molecule HIV-1 fusion inhibitors targeting gp41...
  40. ncbi Luman, a new partner of HIV-1 TMgp41, interferes with Tat-mediated transcription of the HIV-1 LTR
    Guillaume Blot
    Institut Cochin, Département Maladies Infectieuses, Paris F 75014, France
    J Mol Biol 364:1034-47. 2006
    ..The interaction between the TMgp41 subunit of Env and Luman affects the stability of the full-length Luman protein, the precursor of the activated, nuclear form of Luman, which acts negatively on Tat-mediated HIV-1 transactivation...
  41. pmc Structural basis of HIV-1 neutralization by affinity matured Fabs directed against the internal trimeric coiled-coil of gp41
    Elena Gustchina
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 6:e1001182. 2010
    ....
  42. pmc Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation
    S Munir Alam
    Human Vaccine Institute, Duke University Medical Center, 2 Genome Court, P O Box 103020, Durham, NC 27710, USA
    J Virol 85:11725-31. 2011
    ..Thus, these data demonstrate a genetically determined trait that may affect host responses to HIV-1 envelope epitopes recognized by broadly neutralizing antibodies and has implications for unmutated ancestor-based immunogen design...
  43. pmc Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection
    S Munir Alam
    Human Vaccine Institute, Box 3258, Duke University Medical Center, MSRBII Bldg, Room 4042, Durham, NC 27710, USA
    J Virol 82:115-25. 2008
    ....
  44. pmc C-terminal tail of human immunodeficiency virus gp41: functionally rich and structurally enigmatic
    Jonathan D Steckbeck
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Gen Virol 94:1-19. 2013
    ..This review provides an overview of the Env structure and function with a particular emphasis on the CTT and recent studies that highlight its functionally rich nature...
  45. pmc Coupling of human immunodeficiency virus type 1 fusion to virion maturation: a novel role of the gp41 cytoplasmic tail
    Donald J Wyma
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Virol 78:3429-35. 2004
    ..This "inside-out" regulation of HIV-1 fusion could play an important role in the virus life cycle by preventing the entry of immature, noninfectious particles...
  46. pmc Maturation-dependent human immunodeficiency virus type 1 particle fusion requires a carboxyl-terminal region of the gp41 cytoplasmic tail
    Jiyang Jiang
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, A 5301 Medical Center North, Nashville, TN 37232 2363, USA
    J Virol 81:9999-10008. 2007
    ..They further indicate that the stable association of gp41 with Gag in immature virions is not sufficient for inhibition of immature HIV-1 particle fusion...
  47. pmc Truncation of the cytoplasmic domain induces exposure of conserved regions in the ectodomain of human immunodeficiency virus type 1 envelope protein
    Terri G Edwards
    Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Virol 76:2683-91. 2002
    ....
  48. ncbi Dissociation of gp120 from HIV-1 virions induced by soluble CD4
    J P Moore
    Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom
    Science 250:1139-42. 1990
    ..This may represent the initial stage in virus-cell and cell-cell fusion. Shedding of gp120 from virions induced by sCD4 may also contribute to the mechanism by which these soluble receptor molecules neutralize HIV-1...
  49. pmc Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41
    S Moses Dennison
    Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America
    PLoS ONE 6:e27824. 2011
    ..Nonetheless, the Env-liposome prime-boost immunization strategy induced antibodies that recognized a gp41 fusion intermediate protein and was successful in focusing the antibody response to the desired epitope...
  50. ncbi HIV vaccine design and the neutralizing antibody problem
    Dennis R Burton
    Departments of Immunology and Molecular Biology, Scripps Research Institute, La Jolla, California, USA
    Nat Immunol 5:233-6. 2004
  51. pmc Stable docking of neutralizing human immunodeficiency virus type 1 gp41 membrane-proximal external region monoclonal antibodies 2F5 and 4E10 is dependent on the membrane immersion depth of their epitope regions
    S Moses Dennison
    Human Vaccine Institute, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710, USA
    J Virol 83:10211-23. 2009
    ..These data have important implications for the design and use of peptide-liposome conjugates as immunogens for the induction of MPER-neutralizing antibodies...
  52. pmc Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions
    Erin M Scherer
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 107:1529-34. 2010
    ....
  53. pmc Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies
    S Gnanakaran
    Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
    PLoS Comput Biol 6:e1000955. 2010
    ..Five sites were in the CD4-induced coreceptor binding site of gp120, suggesting an important role for this region in the elicitation of broadly neutralizing antibody responses against HIV-1...
  54. pmc Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions
    Sandra Lopez-Verges
    Institut Cochin, Département Maladies Infectieuses, 27 rue du Faubourg Saint Jacques, F 75014 Paris, France
    Proc Natl Acad Sci U S A 103:14947-52. 2006
    ....
  55. pmc Antibody mechanics on a membrane-bound HIV segment essential for GP41-targeted viral neutralization
    Mikyung Kim
    Laboratory of Immunobiology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 18:1235-43. 2011
    ..Hence, target neutralization through this lipid-embedded viral segment places stringent requirements on the plasticity of the antibody combining site...
  56. ncbi Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody
    Micah A Luftig
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Via Pontina Km 30, 600, I 00040 Pomezia Rome, Italy
    Nat Struct Mol Biol 13:740-7. 2006
    ..Thus, our data validate the gp41 N-peptide trimer fusion intermediate as a target for neutralizing antibodies and provide a template for identification of more potent and broadly neutralizing molecules...
  57. pmc Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region
    Gilad Ofek
    Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Virol 84:2955-62. 2010
    ..Together, the results provide a more complete understanding of the 2F5 mechanism of HIV-1 neutralization and indicate ways to enhance the potency of MPER-directed antibodies...
  58. ncbi HIV-1 gp41 fusogenic function triggers autophagy in uninfected cells
    Melanie Denizot
    CPBS, UM1, UM2, CNRS, Institut de Biologie, Montpellier, France
    Autophagy 4:998-1008. 2008
    ....
  59. ncbi Protein design of an HIV-1 entry inhibitor
    M J Root
    Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Science 291:884-8. 2001
    ..The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain...
  60. pmc Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface
    Likai Song
    Cancer Vaccine Center, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:9057-62. 2009
    ..HIV-1 MPER features important for targeted vaccine design have been revealed, the implications of which extend to BNAb targets on other viral fusion proteins...
  61. pmc Redox-triggered infection by disulfide-shackled human immunodeficiency virus type 1 pseudovirions
    James M Binley
    Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Virol 77:5678-84. 2003
    ..Overall, this disulfide-shackled virus is a unique tool with potential utility in vaccine design, drug discovery, and elucidation of the HIV-1 entry process...
  62. pmc The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design
    Marinieve Montero
    Department of Molecular Biology and Chemistry, Simon Fraser University, 8888 University Drive, Burnaby V5A 1S6, British Columbia, Canada
    Microbiol Mol Biol Rev 72:54-84, table of contents. 2008
    ..In addition, emerging approaches to vaccine design are presented...
  63. ncbi Prime boost vaccination approaches with different conjugates of a new HIV-1 gp41 epitope encompassing the membrane proximal external region induce neutralizing antibodies in mice
    Mingkui Zhou
    Georg Speyer Haus, Institute for Biomedical Research, Paul Ehrlich Str 42 44, 60596 Frankfurt, Germany
    Vaccine 30:1911-6. 2012
    ..LS in standardized neutralization assays. Thus, the EC26-2A4 MPER epitope represents a promising vaccine candidate for further analysis in larger animals with respect to the breadth of the neutralizing antibodies induced...
  64. pmc HIV-1 escape from the entry-inhibiting effects of a cholesterol-binding compound via cleavage of gp41 by the viral protease
    Abdul A Waheed
    Virus Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute Frederick, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 104:8467-71. 2007
    ..These data reveal that HIV-1 can escape from an inhibitor of viral entry by acquiring mutations that cause the cytoplasmic tail of gp41 to be cleaved by the viral protease...
  65. pmc Enhancing exposure of HIV-1 neutralization epitopes through mutations in gp41
    Catherine A Blish
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
    PLoS Med 5:e9. 2008
    ..Using a naturally occurring HIV-1 Envelope (Env) variant as a template, we sought to identify features of Env that would enhance exposure of conserved HIV-1 epitopes...
  66. ncbi Intracellular neutralization of HIV transcytosis across tight epithelial barriers by anti-HIV envelope protein dIgA or IgM
    M Bomsel
    U332 INSERM ICGM, Paris, France
    Immunity 9:277-87. 1998
    ..These results suggest that induction of mucosal immunity to HIV envelope proteins may impair the transcytotic route of HIV mucosal transmission...
  67. pmc The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes
    S Munir Alam
    Department of Medicine, Duke Human Vaccine Institute, Duke University School of Medicine, RP1 Circuit Drive, Durham, NC 27710, USA
    J Immunol 178:4424-35. 2007
    ..Taken together, these data demonstrate the similarity of 2F5 and 4E10 mAbs to known anti-cardiolipin Abs and support the model that mAb 2F5 and 4E10 binding to HIV-1 involves both viral lipid membrane and gp41 membrane proximal epitopes...
  68. pmc Antibody neutralization escape mediated by point mutations in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41
    Vandana Kalia
    University of Pittsburgh, Department of Molecular Genetics and Biochemistry, School of Medicine, W1144 BST, Pittsburgh, PA 15261, USA
    J Virol 79:2097-107. 2005
    ....
  69. pmc Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies
    Gary Frey
    Division of Molecular Medicine, Children s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 17:1486-91. 2010
    ..These results have important implications for gp41-based vaccine design...
  70. pmc Maturation-induced cloaking of neutralization epitopes on HIV-1 particles
    Amanda S Joyner
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    PLoS Pathog 7:e1002234. 2011
    ..Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER...
  71. ncbi Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro
    Shu jia Dai
    Laboratory of Metabolism of Biotechnology Derived Drugs, Beijing Institute of Radiation Medicine, Beijing 100850, China
    Acta Pharmacol Sin 26:1274-80. 2005
    ..To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion...
  72. pmc Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates
    Franky Baatz
    Laboratory of Retrovirology, CRP Sante, Luxembourg, Luxembourg
    PLoS ONE 6:e21535. 2011
    ....
  73. pmc Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41
    M B Zwick
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Virol 75:10892-905. 2001
    ..g., subtypes B, C, and E). The results suggest that a rather extensive region of gp41 close to the transmembrane domain is accessible to neutralizing Abs and could form a useful target for vaccine design...
  74. ncbi A trimeric structural subdomain of the HIV-1 transmembrane glycoprotein
    M Lu
    Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA
    J Biomol Struct Dyn 15:465-71. 1997
    ..Our results also provide strong support for the notion that short peptides can form unique, cooperatively folded subdomains, in which elements of secondary structure are stabilized by native-like tertiary interactions...
  75. ncbi Model for the structure of the HIV gp41 ectodomain: insight into the intermolecular interactions of the gp41 loop
    M Caffrey
    Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, Chicago, IL 60612, USA
    Biochim Biophys Acta 1536:116-22. 2001
    ..17 (1998) 4572--4584). The resulting model presents the first structural information for the HIV gp41 loop, which has been implicated to play a direct role in binding to gp120 and C1q of the complement system...
  76. pmc Small molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion
    Gary Frey
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:13938-43. 2006
    ..They bind in a highly conserved, hydrophobic pocket on the inner core of the gp41 trimer, a region previously identified as a potential inhibitor site...
  77. pmc Crystallographic definition of the epitope promiscuity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5: vaccine design implications
    Steve Bryson
    Department of Biochemistry, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    J Virol 83:11862-75. 2009
    ..Based on our results, we propose a somewhat more flexible molecular model of epitope recognition by bnMAb 2F5, which could guide future attempts at designing small-molecule MPER-like vaccines capable of eliciting 2F5-like antibodies...
  78. pmc Human immunodeficiency virus type 1 Env with an intersubunit disulfide bond engages coreceptors but requires bond reduction after engagement to induce fusion
    L G Abrahamyan
    Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois 60612, USA
    J Virol 77:5829-36. 2003
    ..The capture of this configuration of Env could yield a suitable antigen for vaccine development, and it may also be a target for pharmacological intervention against HIV-1 entry...
  79. ncbi Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anion-binding site
    Jean Philippe Julien
    Department of Biochemistry, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    J Mol Biol 384:377-92. 2008
    ....
  80. pmc A V3 loop-dependent gp120 element disrupted by CD4 binding stabilizes the human immunodeficiency virus envelope glycoprotein trimer
    Shi Hua Xiang
    Dana Farber Cancer Institute, 44 Binney Street, CLS 1010, Boston, MA 02115, USA
    J Virol 84:3147-61. 2010
    ..CD4 binding dismantles this element, altering the gp120-gp41 relationship and rendering the hydrophobic patch in the V3 tip available for chemokine receptor binding...
  81. pmc Highly conserved structural properties of the C-terminal tail of HIV-1 gp41 protein despite substantial sequence variation among diverse clades: implications for functions in viral replication
    Jonathan D Steckbeck
    Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 286:27156-66. 2011
    ....
  82. pmc Structure-function analysis of the epitope for 4E10, a broadly neutralizing human immunodeficiency virus type 1 antibody
    Florence M Brunel
    epartments of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, CVN 6, La Jolla, CA 92037, USA
    J Virol 80:1680-7. 2006
    ..Hence, this study represents the first stage toward iterative development of a vaccine based on the 4E10 epitope...
  83. pmc Regulation of human immunodeficiency virus type 1 Env-mediated membrane fusion by viral protease activity
    Tsutomu Murakami
    Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903 0215, Japan
    J Virol 78:1026-31. 2004
    ..Interestingly, truncation of the gp41 cytoplasmic tail reversed the fusion defect. These results suggest that interactions between unprocessed Gag and the gp41 cytoplasmic tail suppress fusion...
  84. pmc Antigenic and immunogenic study of membrane-proximal external region-grafted gp120 antigens by a DNA prime-protein boost immunization strategy
    Mansun Law
    The Scripps Research Institute, Department of Immunology IMM 2, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Virol 81:4272-85. 2007
    ..ii) DNA vaccination with monomeric gp120-based antigens can elicit a consistent NAb response against the homologous neutralization-resistant virus by targeting epitopes outside the V1, V2, and V3 regions...
  85. ncbi A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1
    G Stiegler
    Institute of Applied Microbiology, University of Agricultural Sciences, A 1190 Vienna, Austria
    AIDS Res Hum Retroviruses 17:1757-65. 2001
    ..Moreover, our results suggest that 4E10 should be further investigated for passive anti-HIV immunotherapy...
  86. pmc Rational site-directed mutations of the LLP-1 and LLP-2 lentivirus lytic peptide domains in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41 indicate common functions in cell-cell fusion but distinct roles in virion envelope incorpora
    Vandana Kalia
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Virol 77:3634-46. 2003
    ..Altogether, these results demonstrate for the first time that the highly conserved LLP domains perform critical but distinct functions in Env incorporation and fusogenicity...
  87. pmc Peptides trap the human immunodeficiency virus type 1 envelope glycoprotein fusion intermediate at two sites
    Yong He
    Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Virol 77:1666-71. 2003
    ..These results indicate that there are two distinct sites in receptor-activated Env that are potential targets for drug or vaccine development...
  88. ncbi HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG-seronegative individuals block HIV-1 epithelial transcytosis and neutralize CD4(+) cell infection: an IgA gene and functional analysis
    D Tudor
    Entrée Muqueuse du VIH et Immunité Muqueuse, Mucosal Entry of HIV 1 and Mucosal Immunity, Departement de Biologie Cellulaire, Cell Biology Department, Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Paris, France
    Mucosal Immunol 2:412-26. 2009
    ..This analysis of HEPS monoclonal IgA gives a unique opportunity to correlate an antibody function (resistance to a pathogen in vivo) with an antibody gene. Such neutralizing monoclonal IgAs could be used in microbicide formulation...
  89. pmc Surface exposure of the HIV-1 env cytoplasmic tail LLP2 domain during the membrane fusion process: interaction with gp41 fusion core
    Lu Lu
    Laboratory of Immunology, Department of Biology, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Beijing 100084, China
    J Biol Chem 283:16723-31. 2008
    ..These results suggest that the gp41 CT may interact with the gp41 core, via the surface-exposed LLP2 domain, to regulate Env-mediated membrane fusion...
  90. pmc Novel recombinant engineered gp41 N-terminal heptad repeat trimers and their potential as anti-HIV-1 therapeutics or microbicides
    Xi Chen
    School of Life Sciences, Tsinghua University, Beijing 100084, China
    J Biol Chem 285:25506-15. 2010
    ..Therefore, N28Fd trimer has great potentials for further development as an affordable therapeutic or microbicide for treatment and prevention of HIV-1 infection...
  91. pmc Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41
    Charles Sabin
    Unit of Virus Host Cell Interactions, UMI 3265, Université Joseph Fourier EMBL CNRS, Grenoble, France
    PLoS Pathog 6:e1001195. 2010
    ....
  92. pmc NK cytotoxicity against CD4+ T cells during HIV-1 infection: a gp41 peptide induces the expression of an NKp44 ligand
    Vincent Vieillard
    Laboratoire d Immunologie Cellulaire et Tissulaire, Institut National de la Sante et de la Recherche Medicale U543, Hopital Pitie Salpetriere, 75013 Paris, France
    Proc Natl Acad Sci U S A 102:10981-6. 2005
    ..Understanding this mechanism may help to develop future therapeutic strategies and vaccines against HIV-1 infection...
  93. pmc Direct antibody access to the HIV-1 membrane-proximal external region positively correlates with neutralization sensitivity
    B K Chakrabarti
    IAVI Neutralizing Antibody Center at TSRI, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Virol 85:8217-26. 2011
    ....
  94. pmc Resistance to CCR5 inhibitors caused by sequence changes in the fusion peptide of HIV-1 gp41
    Cleo G Anastassopoulou
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 106:5318-23. 2009
    ..Together, the experimental results and theoretical model may help understand how HIV-1 uses CCR5 to enter target cells under various conditions...
  95. pmc A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies
    Gary Frey
    Laboratory of Molecular Medicine, Children s Hospital, and Department of Pediatrics, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:3739-44. 2008
    ..These results help explain the rarity of 2F5- and 4E10-like antibody responses and suggest a strategy for eliciting them...
  96. pmc Single-particle cryoelectron microscopy analysis reveals the HIV-1 spike as a tripod structure
    Shang Rung Wu
    Department of Biosciences and Nutrition, Karolinska Institute, S 141 83 Huddinge, Sweden
    Proc Natl Acad Sci U S A 107:18844-9. 2010
    ..The loop displacements probably prepared the spike for coreceptor interaction and roof opening so that a new fusion-active gp41 structure, assembled at the center of the cage bottom, could reach the target membrane...
  97. pmc Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution
    Xiaoying Shen
    Department of Surgery, Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 107:5972-7. 2010
    ..These data suggest that a major contribution to the L669S mutant virus phenotype of enhanced susceptibility to MPER mAbs is prolonged exposure of the MPER neutralizing epitope during viral entry...
  98. pmc In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth
    Xiaoying Shen
    Duke Human Vaccine Institute, Duke University Medicine Center, Durham, NC 27710, USA
    J Virol 83:3617-25. 2009
    ..Our findings suggest that multiple events (i.e., genetic predisposition and HIV-1 immune dysregulation) may be required for induction of broadly reactive gp41 MPER antibodies in natural infection...
  99. pmc Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry
    Rachid Sougrat
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 3:e63. 2007
    ..Determination of the molecular composition and structure of the entry claw may facilitate the identification of improved drugs for the inhibition of HIV-1 entry...
  100. pmc Coreceptor tropism can be influenced by amino acid substitutions in the gp41 transmembrane subunit of human immunodeficiency virus type 1 envelope protein
    Wei Huang
    Monogram Biosciences, 345 Oyster Point Blvd, South San Francisco, CA 94080, USA
    J Virol 82:5584-93. 2008
    ..We hypothesize that the latter plays an important role in the transition from CCR5 to CXCR4 coreceptor use...
  101. ncbi Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells
    A G Laurent-Crawford
    Institut Pasteur, Department of AIDS and Retroviruses, UA CNRS 1157, Paris, France
    AIDS Res Hum Retroviruses 9:761-73. 1993
    ..Therefore, cell death during HIV infection in CD4+ lymphocyte cultures is due to a specific event triggered by the gp120-gp41 heterodimer complex programming death in metabolically active cells...

Research Grants72

  1. Rational Design of HIV Fusion Inhibitors Targeting gp41
    Shibo Jiang; Fiscal Year: 2010
    ..Therefore, this research is relevant to public health. ..
  2. SARS-CoV S Protein Receptor-binding Domain-based Vaccines
    Shibo Jiang; Fiscal Year: 2010
    ..The long-term goal of this project is to develop highly effective and safe subunit vaccines for protecting at-risk populations from SARS-CoV infection or bioterrorism attack. ..
  3. Anti-HIV-1 Composite Cellulose Acetate Phthalate Film
    Shibo Jiang; Fiscal Year: 2008
    ....
  4. THE ANTIVIRAL ACTIVITY OF ANTIBODIES TO A FILOVIRUS
    Dennis Burton; Fiscal Year: 2004
    ....
  5. IMMUNOFOCUSING TO A NEUTRALIZING EPITOPE ON GP120
    Dennis Burton; Fiscal Year: 2007
    ..Immunization with this molecule should, in principle, be akin to immunizing with the footprint of b12. [unreadable] [unreadable] [unreadable]..
  6. ANTIBODY EFFECTOR FUNCTION IN PROTECTION AGAINST HIV-1
    Dennis Burton; Fiscal Year: 2007
    ..The results will help clarify how antibodies protect against HIV and may have implications for vaccine design and microbicide development. [unreadable] [unreadable] [unreadable]..
  7. Multivalent gp41 Peptides as Novel Immunogens
    Lai Xi Wang; Fiscal Year: 2004
    ..The structure-immunogenicity relationships will be evaluated. It is expected that the proposed studies will yield important new data with significant relevance to the development of an effective HIV-1 vaccine. ..
  8. NEUTRALIZING ANTIBODIES AGAINST ORTHOPOX VIRUSES
    Dennis Burton; Fiscal Year: 2004
    ..To examine the impact of passive immunization in immunoprophylaxis and immunotherapy of a smallpox-like disease in a non-human primate model, we will use an experimental model of monkeypox virus infection ..
  9. Novel Vaccine Targeting the Sugar Coat of HIV-1
    Lai Xi Wang; Fiscal Year: 2004
    ..The synthetic conjugate-vaccine will be used to immunize mice. The immune responses will be analyzed using ELISAs and virus neutralization assays. ..
  10. Enzymatic Transglycosylation for N-Glycopeptide Synthesis
    Lai Xi Wang; Fiscal Year: 2007
    ..In the long term, the proposed studies will contribute to the development of glycoprotein-based drugs. [unreadable] [unreadable] [unreadable]..
  11. ANTIBODIES AGAINST HIV-1 gp41: TOOLS FOR VACCINE DESIGN
    Michael Zwick; Fiscal Year: 2005
    ..A panel of mAbs against the described epitopes on gp41 will provide valuable tools to aid in HIV-1 vaccine design. ..
  12. COOPERATIVE HUMORAL & CELLULAR IMMUNITY AGAINST HIV/SIV
    Dennis Burton; Fiscal Year: 2005
    ..This will provide us with the first opportunity to look at the effects of potent human mAbs on established infection in the presence of functional T cells. ..
  13. VIRAL EVASION AND HIV ENTRY-BLOCKING STRATEGIES
    Dennis Burton; Fiscal Year: 2004
    ..The studies will reveal how HIV-1 can evade entry-blocking strategies, and may provide important information for vaccine design. ..
  14. ANTI-HIV ANTIBODY IMMUNOTHERAPY IN HUPBL-SCID
    Dennis Burton; Fiscal Year: 2001
    ..The emerging results should assist in the design of immunotherapeutic strategies using neutralizing antibodies and illuminate areas of potential concern such as neutralization escape. ..
  15. Induction of HIV-specific Immune Responses
    Rajesh T Gandhi; Fiscal Year: 2010
    ..By understanding the mechanisms by which immune responses against HIV can be augmented, this may lead to improved ways of treating this disease and may help in developing a vaccine to prevent this infection. ..
  16. HIV-1 entry inhibitors targeting Phe43 cavity in gp120
    Asim Debnath; Fiscal Year: 2003
    ..The long-term goal of this proposal is to optimize the lead compounds through chemical synthesis and structure activity analyses and select 3-4 best compounds for further preclinical studies as novel ianti-HIV-1 chemotherapeutic agents. ..
  17. DESIGN OF NOVEL IMMUNOGENS AND ADJUVANTS FOR HIV VACCINE
    Barton Haynes; Fiscal Year: 2003
    ..abstract_text> ..
  18. Rational Design of CCR5 Antagonists as Anti-HIV-1 Drugs
    Asim Debnath; Fiscal Year: 2006
    ..The long term goal is to optimize the lead compounds through chemical syntheses and structure activity relationship (SAR) analyses and select the 3-4 best compounds for further preclinical studies. ..
  19. HIV-1 Gene Suppression by CD8+ T Cells
    GEORGIA DORIS TOMARAS; Fiscal Year: 2010
    ..The results from this study will determine if induction of noncytolytic CD8 T cells would be beneficial in a protective vaccination strategy or whether it should be restricted to disease-modifying vaccine strategies. ..
  20. MECHANISMS OF T CELL APOPTOSIS DURING HIV1 INFECTION
    Rajesh Gandhi; Fiscal Year: 2002
    ....
  21. UAB AIEDRP: Immune Control and Escape in Acute Infection
    JOHN KILBY; Fiscal Year: 2006
    ..Finally, our proposal involves collaborations with other AIEDRP units where an important exchange of patient specimens, scientific expertise, technology, and data will continue. ..
  22. NCRR FACSAria Cell Sorter
    Barton Haynes; Fiscal Year: 2004
    ..Advisory committees, institutional support, financial support for continued maintenance, and management plans are in place to insure that the instrument will be fully and appropriately utilized. ..
  23. Novel RNase-based Immunotoxin for CD74-positive B-cell Malignancies
    Chien Hsing Chang; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  24. STRUCTURE AND FUNCTION OF ECTO ADPASE/CD39
    Min Lu; Fiscal Year: 2005
    ..This collaboration, based on compelling feasibility data and historical collaborative success, will advance the understanding of CD39 thromboregulation, and lead to a novel therapeutic agent for thrombotic diatheses. ..
  25. Immunologic Control of Drug-resistant HIV-1
    Steven Deeks; Fiscal Year: 2005
    ..Finally, since we will estimate the relative in vivo thresholds for HIV-mediated immunogenicity and pathogenicity, these studies may also have implications for vaccine development. ..
  26. Dynamics of SHIV clade C and S mansoni coinfection
    Ruth Ruprecht; Fiscal Year: 2005
    ..These studies will provide valuable information whether parasitic helminth infections significantly alter HIV/AIDS pathogenesis and/or immunogenicity and efficacy of two different AIDS vaccine strategies. ..
  27. Novel Biological Activities of Anti-Viral Antibody
    Donald Forthal; Fiscal Year: 2006
    ..This project may provide crucial insights for guiding the development of vaccines, immunoprophylaxis and immunotherapy. ..
  28. Functional & Cognitive Impact of HIV in Spanish Speakers
    Mariana Cherner; Fiscal Year: 2008
    ..abstract_text> ..
  29. Pharmacology of Targeted Therapy to Brain Tumors
    FRANCIS SZOKA; Fiscal Year: 2008
    ..These results will provide a rationale for targeted therapies for human brain tumors. ..
  30. Prion Transport Across the Blood-Brain Barrier
    William Banks; Fiscal Year: 2009
    ..To cause disease, prions must cross the blood-brain barrier to enter the brain. We will determine how prions cross the BBB. Knowing how prions enter the brain should lead to strategies on how to prevent prion diseases. ..
  31. Broadly Neutralizing MAbs against Hepatitis C Virus
    William Olson; Fiscal Year: 2008
    ..Current therapies have modest efficacies and significant toxicities, and there is an urgent need for new therapies to combat HCV infection. [unreadable] [unreadable] [unreadable]..
  32. AIDS CLINICAL TRIALS UNIT
    Pablo Tebas; Fiscal Year: 2007
    ..The investigators have credentials in basic and patient-oriented clinical research. ..
  33. MOLECULAR EVOLUTION OF MULTIPLY DELETED SIV IN VIVO
    Ruth Ruprecht; Fiscal Year: 2008
    ..These studies will deepen our understanding of the interaction between the rhesus monkey host, which is susceptible to lentiviral pathogenesis, and Rev-ind nef SIV, an apathogenic virus, even in neonates. ..
  34. Engineered gp41 Peptides as HIV-1 Topical Microbicides
    Min Lu; Fiscal Year: 2009
    ..abstract_text> ..
  35. Poly-functional analyses of vaccine-induced T cell responses
    Guido Ferrari; Fiscal Year: 2010
    ..Overall, these findings will shed new insights on the importance and fate of vaccine-induced T cell responses in controlling HIV-infection. ..
  36. HIV-2 Env Variable Loop Deletions as HIV-1 Vaccines
    George Lin; Fiscal Year: 2006
    ..abstract_text> ..
  37. Novel HIV Neutralizing Human MAbs from Transgenic Mice
    Abraham Pinter; Fiscal Year: 2006
    ....
  38. Novel Inhibitors of HIV-1 Reverse Transcriptase
    BRYAN O HARA; Fiscal Year: 2003
    ..S. If the drug developed has a new mechanism of action, this would further expand the appropriate patient population. ..
  39. TRANSGENIC PRODUCTION OF CD4-IGG2 FOR HIV THERAPY
    William Olson; Fiscal Year: 2004
    ..Success in the project would represent an important milestone for the development both of a new class of anti-HIV-1 therapy and of transgenic technology. ..
  40. Effect of Microbicides on Mucosal HIV Transmission
    Christopher Miller; Fiscal Year: 2004
    ..Further, these studies will determine if individuals that consistently and correctly use of microbicides in the face of repeated viral exposure develop anti-viral immune responses or local infection. ..
  41. Attenuated recombinant Listeria as oral AIDS vaccine
    Ruth Ruprecht; Fiscal Year: 2003
    ..These primate studies represent crucial steps towards developing recombinant Lmdd vectors for clinical trials as oral AIDS vaccine candidates that could be administered easily, even in the developing world. ..
  42. Treatment Intensification for Drug-Resistant HIV
    Steven Deeks; Fiscal Year: 2004
    ..Funding for the pilot clinical trial has been obtained from other sources; funding is requested in this proposal only for costs associated with the measurements of immunologic response to drug-resistant HIV-1. ..
  43. SYNTHETIC GENE CARRIERS TO TREAT CYSTIC FIBROSIS
    FRANCIS SZOKA; Fiscal Year: 2001
    ..abstract_text> ..
  44. NMR STUDIES OF THE HIV ENVELOPE PROTEINS
    Michael Caffrey; Fiscal Year: 2004
    ..In this proposal, a combined approach of molecular biology, biochemistry and NMR spectroscopy will be employed. ..
  45. PTS1 Regulation of Brain Met Enk Levels in Alcoholism
    William Banks; Fiscal Year: 2004
    ..abstract_text> ..
  46. CCR5 Sulfopeptides:A New Class of HIV Entry Inhibitors
    William Olson; Fiscal Year: 2002
    ..This project seeks to develop a novel class of antiretroviral agents using advanced technologies in the areas of peptide chemistry, compound screening, and virology. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE ..
  47. Proteomics of Staphylococcus aureus nasal carriage
    Alexander Cole; Fiscal Year: 2003
    ....
  48. Drug Resistance in Non-Subtype B HIV-1
    Susan Eshleman; Fiscal Year: 2005
    ..abstract_text> ..
  49. FETAL IMMUNOPROPHYLAXIS AGAINST A PRIMATE LENTIVIRUS
    Ruth Ruprecht; Fiscal Year: 2001
    ..Data generated from this work can be translated into human clinical trials aimed at preventing maternal HIV-1 transmission. ..
  50. Radioimmunotherapy of opportunistic infections
    Ekaterina Dadachova; Fiscal Year: 2003
    ..It will also provide some understanding of the fundamentals of interactions between microorganisms and antibodies radiolabeled with particulate-emitting radioisotopes in vitro and in vivo. ..
  51. Humanized PRO 140 for CCR5-Targeted Therapy of HIV
    William Olson; Fiscal Year: 2005
    ..Accordingly, this project will provide important milestones in development of a new class of viral entry inhibitors that target HIV-1 fusion coreceptors. ..
  52. Stabilized gp41 Trimeriration Domains for HIV-1 Vaccine
    Min Lu; Fiscal Year: 2005
    ..Subsequently, we will study the antigen-binding properties of the neutralizing monoclonal antibodies, in order to clarify the nature of gp41-induced antibody response and specific mechanisms for immune evasion. ..
  53. PRO 542 Immunotherapy of Advanced HIV 1 Disease
    William Olson; Fiscal Year: 2005
    ..The overall goal of this project is to expedite development of PRO 542 as the first of a potential new class of inhibitors of HIV-1 attachment. ..
  54. Receptor Binding of Neurotropic HIV Envelopes
    JULIO MARTIN GARCIA; Fiscal Year: 2005
    ....
  55. Novel Chimeric Env Glycoproteins for AIDS Vaccines
    Ling Ye; Fiscal Year: 2005
    ..We will also test the effectiveness of different priming-boosting protocols in eliciting cross-reactive neutralizing antibodies against HIV. ..
  56. PROTECTIVE MECHANISMS WITH ATTENUATED LENTIVIRAL VACCINE
    Christopher Miller; Fiscal Year: 2002
    ....
  57. The impact of early antiretroviral therapy on HIV persistence and inflammation
    STEVEN GRANT DEEKS; Fiscal Year: 2010
    ..Our work may also provide important insights in the role of chronic inflammation in driving viral persistence, and hence may lead to the development of novel interventions. ..
  58. Invasion of C. neoformans into brain endothelial cells
    Ambrose Jong; Fiscal Year: 2008
    ..The information derived from the studies is expected to be helpful in the development of novel strategies to prevent cryptococcal meningitis and its associated morbidity. ..
  59. HIV-1 Glycopeptides as Immunogens
    Lai Xi Wang; Fiscal Year: 2009
    ..Theproposed research attempts to raise broadly neutralizing antibodies through novel immunogen design. Theresearch willyield important new data with direct relevance to HIV-1 vaccine development. ..
  60. Treatment&Pathogenesis of Cerebrospinal Fluid HIV Infect
    Richard Price; Fiscal Year: 2004
    ....
  61. ANTIGENIC PROPERTIES OF THE V1/V2 DOMAIN OF HIV-1 GP120
    Abraham Pinter; Fiscal Year: 2010
    ....
  62. Interactions Between Olive Leaf Extract and HIV Drugs
    Sylvia Lee Huang; Fiscal Year: 2005
    ..We hope that this information will provide an important knowledge base for anti-HIV therapy of OLE alone or in combination with HAART, as well as contribute to our understanding of viral pathogenesis. ..
  63. CSF Molecular Marker Study Consortium
    Richard Price; Fiscal Year: 2006
    ..abstract_text> ..
  64. Development of N-Peptides for Use in HIV-1 Topical Microbicides
    Min Lu; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  65. Rhenium-188 therapy of NIS-expressing breast tumors
    Ekaterina Dadachova; Fiscal Year: 2003
    ..The long-term goal of this research is to contribute to the development of a novel cost-effective radionuclide therapy for treatment of breast cancer and, possibly, for other NIS-expressing cancers such as thyroid cancer. ..
  66. Mechanisms of HIV-1 Transmission in the Genital Mucosa of Women
    Florian Hladik; Fiscal Year: 2008
    ..In this proposal, we will use a novel organ culture model of human vaginal tissue obtained from surgeries to characterize the entry pathways of HIV during the earliest stages of sexual transmission. [unreadable] [unreadable] [unreadable]..
  67. STRUCTURE AND FUNCTION OF THE HIV-1 ENVELOPE PROTEIN
    Min Lu; Fiscal Year: 2008
    ..We wish to elucidate a mechanism for the precise switch between the metastable native and fusogenic forms of the protein. ..
  68. Microbial siderophore-specific innate immune responses
    Roland Strong; Fiscal Year: 2008
    ....
  69. HCV Treatment Cost-Effectiveness in 3 IDU Populations
    BRUCE SCHACKMAN; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  70. Mechanisms of Sexual HIV-1 Transmission
    Florian Hladik; Fiscal Year: 2006
    ..These studies will improve our knowledge of the human genital immune system and shed light on the mechanisms of HIV-l targeting and strain selection in the female genital tract. ..