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Science 19 June 1998:
Vol. 280. no. 5371, pp. 1884 - 1888
DOI: 10.1126/science.280.5371.1884
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Articles

The HIV-1 Envelope Glycoproteins: Fusogens, Antigens, and Immunogens

Richard Wyatt, Joseph Sodroski *

The human immunodeficiency virus-type 1 (HIV-1) envelope glycoproteins interact with receptors on the target cell and mediate virus entry by fusing the viral and cell membranes. The structure of the envelope glycoproteins has evolved to fulfill these functions while evading the neutralizing antibody response. An understanding of the viral strategies for immune evasion should guide attempts to improve the immunogenicity of the HIV-1 envelope glycoproteins and, ultimately, aid in HIV-1 vaccine development.

R. Wyatt is in the Department of Cancer Immunology/AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. J. Sodroski is in the Department of Cancer Immunology/AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: joseph_sodroski{at}dfci.harvard.edu

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Structure of the Fab Fragment of F105, a Broadly Reactive Anti-Human Immunodeficiency Virus (HIV) Antibody That Recognizes the CD4 Binding Site of HIV Type 1 gp120.
R. A. Wilkinson, C. Piscitelli, M. Teintze, L. A. Cavacini, M. R. Posner, and C. M. Lawrence (2005)
J. Virol. 79, 13060-13069
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Inhibition of Coreceptor-Independent Cell-to-Cell Human Immunodeficiency Virus Type 1 Transmission by a CD4-Immunoglobulin G2 Fusion Protein.
B. Bosch, J. Blanco, E. Pauls, I. Clotet-Codina, M. Armand-Ugon, B. Grigorov, D. Muriaux, B. Clotet, J.-L. Darlix, and J. A. Este (2005)
Antimicrob. Agents Chemother. 49, 4296-4304
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Stoichiometry of Envelope Glycoprotein Trimers in the Entry of Human Immunodeficiency Virus Type 1.
X. Yang, S. Kurteva, X. Ren, S. Lee, and J. Sodroski (2005)
J. Virol. 79, 12132-12147
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Biochemical and Immunogenic Characterization of Soluble Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Expressed by Semliki Forest Virus.
M. N. E. Forsell, Y. Li, M. Sundback, K. Svehla, P. Liljestrom, J. R. Mascola, R. Wyatt, and G. B. K. Hedestam (2005)
J. Virol. 79, 10902-10914
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Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies.
M. Li, F. Gao, J. R. Mascola, L. Stamatatos, V. R. Polonis, M. Koutsoukos, G. Voss, P. Goepfert, P. Gilbert, K. M. Greene, et al. (2005)
J. Virol. 79, 10108-10125
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Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis.
M. Pancera, J. Lebowitz, A. Schon, P. Zhu, E. Freire, P. D. Kwong, K. H. Roux, J. Sodroski, and R. Wyatt (2005)
J. Virol. 79, 9954-9969
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Evaluating the Immunogenicity of a Disulfide-Stabilized, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1.
S. Beddows, N. Schulke, M. Kirschner, K. Barnes, M. Franti, E. Michael, T. Ketas, R. W. Sanders, P. J. Maddon, W. C. Olson, et al. (2005)
J. Virol. 79, 8812-8827
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The V1, V2, and V3 Regions of the Human Immunodeficiency Virus Type 1 Envelope Differentially Affect the Viral Phenotype in an Isolate-Dependent Manner.
C. J. Saunders, R. A. McCaffrey, I. Zharkikh, Z. Kraft, S. E. Malenbaum, B. Burke, C. Cheng-Mayer, and L. Stamatatos (2005)
J. Virol. 79, 9069-9080
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Design, Expression, and Immunogenicity of a Soluble HIV Trimeric Envelope Fragment Adopting a Prefusion gp41 Configuration.
Z.-S. Qiao, M. Kim, B. Reinhold, D. Montefiori, J.-h. Wang, and E. L. Reinherz (2005)
J. Biol. Chem. 280, 23138-23146
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Enhanced Immunogenicity of gp120 Protein When Combined with Recombinant DNA Priming To Generate Antibodies That Neutralize the JR-FL Primary Isolate of Human Immunodeficiency Virus Type 1.
S. Wang, J. Arthos, J. M. Lawrence, D. Van Ryk, I. Mboudjeka, S. Shen, T.-h. W. Chou, D. C. Montefiori, and S. Lu (2005)
J. Virol. 79, 7933-7937
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Heparan Sulfate Targets the HIV-1 Envelope Glycoprotein gp120 Coreceptor Binding Site.
R. R. Vives, A. Imberty, Q. J. Sattentau, and H. Lortat-Jacob (2005)
J. Biol. Chem. 280, 21353-21357
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Cryptic Nature of a Conserved, CD4-Inducible V3 Loop Neutralization Epitope in the Native Envelope Glycoprotein Oligomer of CCR5-Restricted, but Not CXCR4-Using, Primary Human Immunodeficiency Virus Type 1 Strains.
P. Lusso, P. L. Earl, F. Sironi, F. Santoro, C. Ripamonti, G. Scarlatti, R. Longhi, E. A. Berger, and S. E. Burastero (2005)
J. Virol. 79, 6957-6968
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Antigenic conservation and immunogenicity of the HIV coreceptor binding site.
J. M. Decker, F. Bibollet-Ruche, X. Wei, S. Wang, D. N. Levy, W. Wang, E. Delaporte, M. Peeters, C. A. Derdeyn, S. Allen, et al. (2005)
J. Exp. Med. 201, 1407-1419
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An Unrelated Monoclonal Antibody Neutralizes Human Immunodeficiency Virus Type 1 by Binding to an Artificial Epitope Engineered in a Functionally Neutral Region of the Viral Envelope Glycoproteins.
X. Ren, J. Sodroski, and X. Yang (2005)
J. Virol. 79, 5616-5624
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Multiple and multivalent interactions of novel anti-AIDS drug candidates, sulfated polymannuronate (SPMG)-derived oligosaccharides, with gp120 and their anti-HIV activities.
H. Liu, M. Geng, X. Xin, F. Li, Z. Zhang, J. Li, and J. Ding (2005)
Glycobiology 15, 501-510
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Variants of Human Immunodeficiency Virus Type 1 That Efficiently Use CCR5 Lacking the Tyrosine-Sulfated Amino Terminus Have Adaptive Mutations in gp120, Including Loss of a Functional N-Glycan.
E. J. Platt, D. M. Shea, P. P. Rose, and D. Kabat (2005)
J. Virol. 79, 4357-4368
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Galectin-1 Acts as a Soluble Host Factor That Promotes HIV-1 Infectivity through Stabilization of Virus Attachment to Host Cells.
M. Ouellet, S. Mercier, I. Pelletier, S. Bounou, J. Roy, J. Hirabayashi, S. Sato, and M. J. Tremblay (2005)
J. Immunol. 174, 4120-4126
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The CCR5 Receptor-Based Mechanism of Action of 873140, a Potent Allosteric Noncompetitive HIV Entry Inhibitor.
C. Watson, S. Jenkinson, W. Kazmierski, and T. Kenakin (2005)
Mol. Pharmacol. 67, 1268-1282
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Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1.
X. Yang, S. Kurteva, S. Lee, and J. Sodroski (2005)
J. Virol. 79, 3500-3508
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Trimeric Membrane-anchored gp41 Inhibits HIV Membrane Fusion.
O. Lenz, M. T. Dittmar, A. Wagner, B. Ferko, K. Vorauer-Uhl, G. Stiegler, and W. Weissenhorn (2005)
J. Biol. Chem. 280, 4095-4101
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Surface Stability and Immunogenicity of the Human Immunodeficiency Virus Envelope Glycoprotein: Role of the Cytoplasmic Domain.
L. Ye, Z. Bu, A. Vzorov, D. Taylor, R. W. Compans, and C. Yang (2004)
J. Virol. 78, 13409-13419
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CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes.
K. Balabanian, J. Harriague, C. Decrion, B. Lagane, S. Shorte, F. Baleux, J.-L. Virelizier, F. Arenzana-Seisdedos, and L. A. Chakrabarti (2004)
J. Immunol. 173, 7150-7160
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Characterization of the Outer Domain of the gp120 Glycoprotein from Human Immunodeficiency Virus Type 1.
X. Yang, V. Tomov, S. Kurteva, L. Wang, X. Ren, M. K. Gorny, S. Zolla-Pazner, and J. Sodroski (2004)
J. Virol. 78, 12975-12986
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Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin.
M. Zhang, B. Gaschen, W. Blay, B. Foley, N. Haigwood, C. Kuiken, and B. Korber (2004)
Glycobiology 14, 1229-1246
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Evolutionary Dynamics of the Glycan Shield of the Human Immunodeficiency Virus Envelope during Natural Infection and Implications for Exposure of the 2G12 Epitope.
L. Dacheux, A. Moreau, Y. Ataman-Onal, F. Biron, B. Verrier, and F. Barin (2004)
J. Virol. 78, 12625-12637
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Infection of Specific Dendritic Cells by CCR5-Tropic Human Immunodeficiency Virus Type 1 Promotes Cell-Mediated Transmission of Virus Resistant to Broadly Neutralizing Antibodies.
L. Ganesh, K. Leung, K. Lore, R. Levin, A. Panet, O. Schwartz, R. A. Koup, and G. J. Nabel (2004)
J. Virol. 78, 11980-11987
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A Nonneutralizing Anti-HIV-1 Antibody Turns into a Neutralizing Antibody When Expressed on the Surface of HIV-1-Susceptible Cells: A New Way to Fight HIV.
S.-J. Lee, L. Garza, J. Yao, A. L. Notkins, and P. Zhou (2004)
J. Immunol. 173, 4618-4626
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