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Science 19 June 1998:
Vol. 280. no. 5371, pp. 1949 - 1953
DOI: 10.1126/science.280.5371.1949
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Reports

A Conserved HIV gp120 Glycoprotein Structure Involved in Chemokine Receptor Binding

Carlo D. Rizzuto, Richard Wyatt, Nivia Hernández-Ramos, Ying Sun, Peter D. Kwong, Wayne A. Hendrickson, Joseph Sodroski *

The entry of primate immunodeficiency viruses into target cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors, CD4 and members of the chemokine receptor family. The gp120 third variable (V3) loop has been implicated in chemokine receptor binding, but the use of the CCR5 chemokine receptor by diverse primate immunodeficiency viruses suggests the involvement of an additional, conserved gp120 element. Through the use of gp120 mutants, a highly conserved gp120 structure was shown to be critical for CCR5 binding. This structure is located adjacent to the V3 loop and contains neutralization epitopes induced by CD4 binding. This conserved element may be a useful target for pharmacologic or prophylactic intervention in human immunodeficiency virus (HIV) infections.

C. D. Rizzuto, R. Wyatt, N. Hernández-Ramos, Y. Sun, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
P. D. Kwong and W. A. Hendrickson, Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
J. Sodroski, Department of Cancer Immunology and 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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   Abstract »    Full Text »    PDF »
Neutralization of Infectivity of Diverse R5 Clinical Isolates of Human Immunodeficiency Virus Type 1 by gp120-Binding 2'F-RNA Aptamers.
M. Khati, M. Schuman, J. Ibrahim, Q. Sattentau, S. Gordon, and W. James (2003)
J. Virol. 77, 12692-12698
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Covalently Linked Human Immunodeficiency Virus Type 1 gp120/gp41 Is Stably Anchored in Rhabdovirus Particles and Exposes Critical Neutralizing Epitopes.
P. M. McKenna, R. J. Pomerantz, B. Dietzschold, J. P. McGettigan, and M. J. Schnell (2003)
J. Virol. 77, 12782-12794
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Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS.
A. Ohagen, A. Devitt, K. J. Kunstman, P. R. Gorry, P. P. Rose, B. Korber, J. Taylor, R. Levy, R. L. Murphy, S. M. Wolinsky, et al. (2003)
J. Virol. 77, 12336-12345
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The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4+ T cell-depleted rhesus monkeys.
T. Igarashi, H. Imamichi, C. R. Brown, V. M. Hirsch, and M. A. Martin (2003)
J. Leukoc. Biol. 74, 772-780
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Functional Evolution of the HIV-1 Envelope Glycoprotein 120 Association Site of Glycoprotein 41.
P. Poumbourios, A. L. Maerz, and H. E. Drummer (2003)
J. Biol. Chem. 278, 42149-42160
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Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1.
A. F. Labrijn, P. Poignard, A. Raja, M. B. Zwick, K. Delgado, M. Franti, J. Binley, V. Vivona, C. Grundner, C.-C. Huang, et al. (2003)
J. Virol. 77, 10557-10565
   Abstract »    Full Text »    PDF »
The entry of entry inhibitors: A fusion of science and medicine.
J. P. Moore and R. W. Doms (2003)
PNAS 100, 10598-10602
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Multiple Interactions across the Surface of the gp120 Core Structure Determine the Global Neutralization Resistance Phenotype of Human Immunodeficiency Virus Type 1.
P. Bouma, M. Leavitt, P. F. Zhang, I. A. Sidorov, D. S. Dimitrov, and G. V. Quinnan Jr. (2003)
J. Virol. 77, 8061-8071
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A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12.
M. B. Zwick, R. Kelleher, R. Jensen, A. F. Labrijn, M. Wang, G. V. Quinnan Jr., P. W. H. I. Parren, and D. R. Burton (2003)
J. Virol. 77, 6965-6978
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Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design.
R. Pantophlet, I. A. Wilson, and D. R. Burton (2003)
J. Virol. 77, 5889-5901
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Retrocyclin, an Antiretroviral {theta}-Defensin, Is a Lectin.
W. Wang, A. M. Cole, T. Hong, A. J. Waring, and R. I. Lehrer (2003)
J. Immunol. 170, 4708-4716
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The LLSGIV stretch of the N-terminal region of HIV-1 gp41 is critical for binding to a model peptide, T20.
V. D. Trivedi, S.-F. Cheng, C.-W. Wu, R. Karthikeyan, C.-J. Chen, and D.-K. Chang (2003)
Protein Eng. Des. Sel. 16, 311-317
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Type 1 Infection and Replication in Normal Human Oral Keratinocytes.
X. Liu, J. Zha, H. Chen, J. Nishitani, P. Camargo, S. W. Cole, and J. A. Zack (2003)
J. Virol. 77, 3470-3476
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Effect of Amino Acid Substitution of the V3 and Bridging Sheet Residues in Human Immunodeficiency Virus Type 1 Subtype C gp120 on CCR5 Utilization.
P. Suphaphiphat, A. Thitithanyanont, S. Paca-Uccaralertkun, M. Essex, and T.-H. Lee (2003)
J. Virol. 77, 3832-3837
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Neutralization of Human Immunodeficiency Virus Type 1 by sCD4-17b, a Single-Chain Chimeric Protein, Based on Sequential Interaction of gp120 with CD4 and Coreceptor.
B. Dey, C. S. Del Castillo, and E. A. Berger (2003)
J. Virol. 77, 2859-2865
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Identification of a Receptor-Binding Domain of the Spike Glycoprotein of Human Coronavirus HCoV-229E.
A. Bonavia, B. D. Zelus, D. E. Wentworth, P. J. Talbot, and K. V. Holmes (2003)
J. Virol. 77, 2530-2538
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Identification of gp120 Binding Sites on CXCR4 by Using CD4-Independent Human Immunodeficiency Virus Type 2 Env Proteins.
G. Lin, F. Baribaud, J. Romano, R. W. Doms, and J. A. Hoxie (2002)
J. Virol. 77, 931-942
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Increased Mucosal Transmission but Not Enhanced Pathogenicity of the CCR5-Tropic, Simian AIDS-Inducing Simian/Human Immunodeficiency Virus SHIVSF162P3 Maps to Envelope gp120.
M. Hsu, J. M. Harouse, A. Gettie, C. Buckner, J. Blanchard, and C. Cheng-Mayer (2002)
J. Virol. 77, 989-998
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Inhibitors of Protein-Disulfide Isomerase Prevent Cleavage of Disulfide Bonds in Receptor-bound Glycoprotein 120 and Prevent HIV-1 Entry.
A. Gallina, T. M. Hanley, R. Mandel, M. Trahey, C. C. Broder, G. A. Viglianti, and H. J.-P. Ryser (2002)
J. Biol. Chem. 277, 50579-50588
   Abstract »    Full Text »    PDF »
Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics.
J. D. Reeves, S. A. Gallo, N. Ahmad, J. L. Miamidian, P. E. Harvey, M. Sharron, S. Pohlmann, J. N. Sfakianos, C. A. Derdeyn, R. Blumenthal, et al. (2002)
PNAS 99, 16249-16254
   Abstract »    Full Text »    PDF »
Amino acid deletions are introduced into the V2 region of gp120 during independent pathogenic simian immunodeficiency virus/HIV chimeric virus (SHIV) infections of rhesus monkeys generating variants that are macrophage tropic.
H. Imamichi, T. Igarashi, T. Imamichi, O. K. Donau, Y. Endo, Y. Nishimura, R. L. Willey, A. F. Suffredini, H. C. Lane, and M. A. Martin (2002)
PNAS 99, 13813-13818
   Abstract »    Full Text »    PDF »
Rescue of HIV-1 Receptor Function through Cooperation between Different Forms of the CCR5 Chemokine Receptor.
M. Chelli and M. Alizon (2002)
J. Biol. Chem. 277, 39388-39396
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Identification of Conserved and Variable Structures in the Human Immunodeficiency Virus gp120 Glycoprotein of Importance for CXCR4 Binding.
S. Basmaciogullari, G. J. Babcock, D. Van Ryk, W. Wojtowicz, and J. Sodroski (2002)
J. Virol. 76, 10791-10800
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Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein.
S.-H. Xiang, P. D. Kwong, R. Gupta, C. D. Rizzuto, D. J. Casper, R. Wyatt, L. Wang, W. A. Hendrickson, M. L. Doyle, and J. Sodroski (2002)
J. Virol. 76, 9888-9899
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Human Monoclonal Antibodies Specific for Conformation-Sensitive Epitopes of V3 Neutralize Human Immunodeficiency Virus Type 1 Primary Isolates from Various Clades.
M. K. Gorny, C. Williams, B. Volsky, K. Revesz, S. Cohen, V. R. Polonis, W. J. Honnen, S. C. Kayman, C. Krachmarov, A. Pinter, et al. (2002)
J. Virol. 76, 9035-9045
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Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1.
R. W. Sanders, M. Vesanen, N. Schuelke, A. Master, L. Schiffner, R. Kalyanaraman, M. Paluch, B. Berkhout, P. J. Maddon, W. C. Olson, et al. (2002)
J. Virol. 76, 8875-8889
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Efficient Isolation of Novel Human Monoclonal Antibodies with Neutralizing Activity Against HIV-1 from Transgenic Mice Expressing Human Ig Loci.
Y. He, W. J. Honnen, C. P. Krachmarov, M. Burkhart, S. C. Kayman, J. Corvalan, and A. Pinter (2002)
J. Immunol. 169, 595-605
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Comparison of Predicted Scaffold-Compatible Sequence Variation in the Triple-Hairpin Structure of Human Immunodeficiency Virus Type 1 gp41 with Patient Data.
N. Boutonnet, W. Janssens, C. Boutton, J.-L. Verschelde, L. Heyndrickx, E. Beirnaert, G. van der Groen, and I. Lasters (2002)
J. Virol. 76, 7595-7606
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