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PMID: 15731244 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Stoichiometry of antibody neutralization of human immunodeficiency virus type 1.

Journal of virology ·Vol. 79 ·No. 6 ·2005-03-00 ·Pages 3500-8

Yang X, Kurteva S, Lee S, Sodroski J

Abstract

The human immunodeficiency virus envelope glycoproteins function as trimers on the viral surface, where they are targeted by neutralizing antibodies. Different monoclonal antibodies neutralize human immunodeficiency virus type 1 (HIV-1) infectivity by binding to structurally and functionally distinct moieties on the envelope glycoprotein trimer. By measuring antibody neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins, we demonstrate that the HIV-1 envelope glycoprotein trimer is inactivated by the binding of a single antibody molecule. Virus neutralization requires essentially all of the functional trimers to be occupied by at least one antibody. This model applies to antibodies differing in neutralizing potency and to virus isolates with various neutralization sensitivities. Understanding these requirements for HIV-1 neutralization by antibodies will assist in establishing goals for an effective AIDS vaccine.

MeSH Terms
Antibodies, Monoclonal/immunology Antigen-Antibody Reactions Binding Sites, Antibody Gene Products, env/immunology HIV Antibodies/immunology HIV Antigens HIV-1/immunology Neutralization Tests Viral Envelope Proteins/immunology
Chemicals
Antibodies, Monoclonal Gene Products, env HIV Antibodies HIV Antigens Viral Envelope Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yang Xinzhen
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, JFB-609, 44 Binney St., Boston, MA 02115, USA. Xinzhen_Yang@dfci.harvard.edu
Kurteva Svetla
Lee Sandra
Sodroski Joseph
References (84)
84 references, click to expand
  1. Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1.
    J Virol. 2000 Aug;74(15):7005-15 PMID: 10888639
  2. Cooperative subunit interactions within the oligomeric envelope glycoprotein of HIV-1: functional complementation of specific defects in gp120 and gp41.
    Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12794-9 PMID: 11050186
  3. Improved elicitation of neutralizing antibodies against primary human immunodeficiency viruses by soluble stabilized envelope glycoprotein trimers.
    J Virol. 2001 Feb;75(3):1165-71 PMID: 11152489
  4. Membrane fusion mechanisms: the influenza hemagglutinin paradigm and its implications for intracellular fusion.
    Traffic. 2000 Aug;1(8):598-604 PMID: 11208147
  5. Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein.
    J Virol. 1993 May;67(5):2747-55 PMID: 8474172
  6. Legitimate and illegitimate cleavage of human immunodeficiency virus glycoproteins by furin.
    J Virol. 1993 Jun;67(6):3601-4 PMID: 8497067
  7. Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding.
    J Virol. 1993 Jul;67(7):3978-88 PMID: 7685405
  8. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1.
    J Virol. 1993 Nov;67(11):6642-7 PMID: 7692082
  9. Formation of mixed hemagglutinin trimers in the course of double infection with influenza viruses belonging to different subtypes.
    Virus Res. 1988 May;10(2-3):153-65 PMID: 3414181
  10. Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160.
    Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 PMID: 2849111
  11. Identification of conserved and variant epitopes of human immunodeficiency virus type 1 (HIV-1) gp120 by human monoclonal antibodies produced by EBV-transformed cell lines.
    AIDS Res Hum Retroviruses. 1990 May;6(5):567-79 PMID: 1694449
  12. Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8597-601 PMID: 1700435
  13. Dissociation of gp120 from HIV-1 virions induced by soluble CD4.
    Science. 1990 Nov 23;250(4984):1139-42 PMID: 2251501
  14. Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein.
    J Virol. 1991 Apr;65(4):2047-55 PMID: 1900540
  15. Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes.
    J Virol. 1991 Aug;65(8):3973-85 PMID: 1830110
  16. Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody.
    J Virol. 1991 Nov;65(11):6188-93 PMID: 1717717
  17. Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus.
    Virology. 1992 Aug;189(2):695-714 PMID: 1386485
  18. Morphological estimation of total number of influenza A type virion spikes.
    J Electron Microsc (Tokyo). 1992 Apr;41(2):104-6 PMID: 1506801
  19. Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation.
    J Virol. 1992 Nov;66(11):6587-600 PMID: 1404605
  20. Neutralization of HIV-1 by F105, a human monoclonal antibody to the CD4 binding site of gp120.
    J Acquir Immune Defic Syndr. 1993 Jan;6(1):7-14 PMID: 8417177
  21. Morphometric analysis of envelope glycoprotein gp120 distribution on HIV-1 virions.
    J Histochem Cytochem. 1993 Feb;41(2):265-71 PMID: 7678271
  22. Single- and multi-hit kinetics of immunoglobulin G neutralization of human immunodeficiency virus type 1 by monoclonal antibodies.
    J Gen Virol. 1994 Jun;75 ( Pt 6):1457-60 PMID: 8207410
  23. The ratio of defective HIV-1 particles to replication-competent infectious virions.
    Acta Virol. 1994 Feb;38(1):59-61 PMID: 7520666
  24. Determination of the size of HIV using adenovirus type 2 as an internal length marker.
    J Virol Methods. 1994 Jun;48(1):43-52 PMID: 7962259
  25. Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies.
    J Virol. 1994 Dec;68(12):8350-64 PMID: 7525988
  26. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody.
    Science. 1994 Nov 11;266(5187):1024-7 PMID: 7973652
  27. Competitive binding of neutralizing monoclonal and polyclonal IgG to the HA of influenza A virions in solution: only one IgG molecule is bound per HA trimer regardless of the specificity of the competitor.
    Virology. 1994 Nov 15;205(1):360-3 PMID: 7975232
  28. Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG.
    J Virol. 1995 Nov;69(11):6609-17 PMID: 7474069
  29. Quantitative analysis of serum neutralization of human immunodeficiency virus type 1 from subtypes A, B, C, D, E, F, and I: lack of direct correlation between neutralization serotypes and genetic subtypes and evidence for prevalent serum-dependent infectivity enhancement.
    J Virol. 1996 Jan;70(1):445-58 PMID: 8523557
  30. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1.
    J Virol. 1996 Feb;70(2):1100-8 PMID: 8551569
  31. Differential role of V3-specific antibodies in neutralization assays involving primary and laboratory-adapted isolates of HIV type 1.
    AIDS Res Hum Retroviruses. 1995 Nov;11(11):1379-91 PMID: 8573396
  32. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein.
    J Virol. 1996 Mar;70(3):1863-72 PMID: 8627711
  33. Neutralizing antibodies to human immunodeficiency virus type-1 gp120 induce envelope glycoprotein subunit dissociation.
    J Exp Med. 1996 Feb 1;183(2):473-84 PMID: 8627160
  34. Folding, assembly, and intracellular trafficking of the human immunodeficiency virus type 1 envelope glycoprotein analyzed with monoclonal antibodies recognizing maturational intermediates.
    J Virol. 1996 Jun;70(6):3407-15 PMID: 8648672
  35. Membrane fusion mediated by the influenza virus hemagglutinin requires the concerted action of at least three hemagglutinin trimers.
    J Cell Biol. 1996 May;133(3):559-69 PMID: 8636231
  36. The fusion kinetics of influenza hemagglutinin expressing cells to planar bilayer membranes is affected by HA density and host cell surface.
    J Gen Physiol. 1995 Nov;106(5):783-802 PMID: 8648292
  37. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1.
    Nature. 1996 Aug 29;382(6594):833-5 PMID: 8752281
  38. Dilation of the influenza hemagglutinin fusion pore revealed by the kinetics of individual cell-cell fusion events.
    J Cell Biol. 1996 Oct;135(1):63-71 PMID: 8858163
  39. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5.
    Nature. 1996 Nov 14;384(6605):184-7 PMID: 8906796
  40. Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals.
    J Virol. 1997 May;71(5):3734-41 PMID: 9094648
  41. Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys.
    J Virol. 1997 Jun;71(6):4218-25 PMID: 9151808
  42. HIV type 1 coreceptors, neutralization serotypes, and vaccine development.
    AIDS Res Hum Retroviruses. 1997 Jun 10;13(9):733-6 PMID: 9171216
  43. A model for neutralization of viruses based on antibody coating of the virion surface.
    Curr Top Microbiol Immunol. 2001;260:109-43 PMID: 11443871
  44. Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1.
    Virology. 2001 Jul 20;286(1):45-53 PMID: 11448157
  45. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro.
    J Virol. 2001 Sep;75(17):8340-7 PMID: 11483779
  46. Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6.
    J Virol. 2001 Oct;75(19):9177-86 PMID: 11533181
  47. The stoichiometry of trimeric SIV glycoprotein interaction with CD4 differs from that of anti-envelope antibody Fab fragments.
    J Biol Chem. 2001 Nov 16;276(46):42667-76 PMID: 11544255
  48. Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies.
    J Virol. 2001 Dec;75(24):12198-208 PMID: 11711611
  49. Envelope glycoprotein incorporation, not shedding of surface envelope glycoprotein (gp120/SU), Is the primary determinant of SU content of purified human immunodeficiency virus type 1 and simian immunodeficiency virus.
    J Virol. 2002 Jun;76(11):5315-25 PMID: 11991960
  50. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120.
    J Virol. 2002 Jul;76(14):7293-305 PMID: 12072528
  51. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1-->2 mannose residues on the outer face of gp120.
    J Virol. 2002 Jul;76(14):7306-21 PMID: 12072529
  52. Human monoclonal antibodies specific for conformation-sensitive epitopes of V3 neutralize human immunodeficiency virus type 1 primary isolates from various clades.
    J Virol. 2002 Sep;76(18):9035-45 PMID: 12186887
  53. Mechanism of neutralization of influenza virus infectivity by antibodies.
    Virology. 2002 Oct 25;302(2):294-8 PMID: 12441073
  54. Heterogeneity of envelope molecules expressed on primary human immunodeficiency virus type 1 particles as probed by the binding of neutralizing and nonneutralizing antibodies.
    J Virol. 2003 Jan;77(1):353-65 PMID: 12477840
  55. Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site.
    J Virol. 2003 Jan;77(2):1084-91 PMID: 12502824
  56. Effects of HIV type 1 envelope glycoprotein proteolytic processing on antigenicity.
    AIDS Res Hum Retroviruses. 2003 Mar;19(3):217-26 PMID: 12689414
  57. Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15812-7 PMID: 14668432
  58. Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D.
    Structure. 2004 Feb;12(2):193-204 PMID: 14962380
  59. HIV vaccine design and the neutralizing antibody problem.
    Nat Immunol. 2004 Mar;5(3):233-6 PMID: 14985706
  60. Modulation of Env content in virions of simian immunodeficiency virus: correlation with cell surface expression and virion infectivity.
    J Virol. 2004 Jul;78(13):6775-85 PMID: 15194752
  61. AIDS/HIV. Developing an AIDS vaccine: need, uncertainty, hope.
    Science. 2004 Jun 25;304(5679):1913-4 PMID: 15218131
  62. Electron microscopy of influenza virus.
    Br Med Bull. 1979 Jan;35(1):35-8 PMID: 367484
  63. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS.
    Cell. 1986 Jun 6;45(5):637-48 PMID: 2423250
  64. Shedding and interspecies type sero-reactivity of the envelope glycopolypeptide gp120 of the human immunodeficiency virus.
    J Gen Virol. 1986 Nov;67 ( Pt 11):2533-8 PMID: 2431105
  65. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions.
    J Virol. 1987 Feb;61(2):570-8 PMID: 2433466
  66. Quantitative relationships between an influenza virus and neutralizing antibody.
    Virology. 1987 Aug;159(2):288-98 PMID: 3617501
  67. Posttranslational oligomerization and cooperative acid activation of mixed influenza hemagglutinin trimers.
    J Cell Biol. 1988 Mar;106(3):629-39 PMID: 3279048
  68. The organization of the envelope projections on the surface of HIV.
    Arch Virol. 1988;100(3-4):255-66 PMID: 3401118
  69. Human monoclonal antibodies to the V3 loop of HIV-1 with intra- and interclade cross-reactivity.
    J Immunol. 1997 Nov 15;159(10):5114-22 PMID: 9366441
  70. Passage of HIV-1 molecular clones into different cell lines confers differential sensitivity to neutralization.
    Virology. 1997 Nov 24;238(2):254-64 PMID: 9400598
  71. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity.
    J Virol. 1998 May;72(5):3512-9 PMID: 9557629
  72. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens.
    Science. 1998 Jun 19;280(5371):1884-8 PMID: 9632381
  73. The antigenic structure of the HIV gp120 envelope glycoprotein.
    Nature. 1998 Jun 18;393(6686):705-11 PMID: 9641684
  74. Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies.
    J Virol. 1998 Aug;72(8):6332-8 PMID: 9658072
  75. Neutralization profiles of primary human immunodeficiency virus type 1 isolates in the context of coreceptor usage.
    J Virol. 1998 Sep;72(9):6988-96 PMID: 9696790
  76. Antibody neutralization-resistant primary isolates of human immunodeficiency virus type 1.
    J Virol. 1998 Dec;72(12):10270-4 PMID: 9811774
  77. Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys.
    Nat Med. 1999 Feb;5(2):204-10 PMID: 9930869
  78. Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses.
    Virology. 1999 Mar 30;256(1):15-21 PMID: 10087222
  79. Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies.
    J Virol. 1999 May;73(5):4009-18 PMID: 10196297
  80. Stoichiometry of monoclonal antibody neutralization of T-cell line-adapted human immunodeficiency virus type 1.
    J Virol. 1999 Oct;73(10):8364-70 PMID: 10482587
  81. Characterization of primary isolate-like variants of simian-human immunodeficiency virus.
    J Virol. 1999 Dec;73(12):10199-207 PMID: 10559336
  82. Minimal aggregate size and minimal fusion unit for the first fusion pore of influenza hemagglutinin-mediated membrane fusion.
    Biophys J. 2000 Jan;78(1):227-45 PMID: 10620288
  83. Oligomeric modeling and electrostatic analysis of the gp120 envelope glycoprotein of human immunodeficiency virus.
    J Virol. 2000 Feb;74(4):1961-72 PMID: 10644369
  84. Fine definition of a conserved CCR5-binding region on the human immunodeficiency virus type 1 glycoprotein 120.
    AIDS Res Hum Retroviruses. 2000 May 20;16(8):741-9 PMID: 10826481
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.6.3500-3508.2005
Email
xinzhen_yang@dfci.harvard.edu
Published
2005-03-00
Pages
3500-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1075697
Subset
IM
Grants
NIAID NIH HHS · R37 AI024755 · United States
NIAID NIH HHS · AI31783 · United States
NIAID NIH HHS · R01 AI031783 · United States
NIAID NIH HHS · U01 AI046725 · United States
NIAID NIH HHS · AI46725 · United States
NIAID NIH HHS · AI24755 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1128/JVI.79.6.3500-3508.2005 PMC Full Text View journal details
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