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Science 11 September 1987:
Vol. 237. no. 4820, pp. 1351 - 1355
DOI: 10.1126/science.3629244
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Articles

Science, Vol 237, Issue 4820, 1351-1355
Copyright © 1987 by American Association for the Advancement of Science

articles

Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1

M Kowalski, J Potz, L Basiripour, T Dorfman, WC Goh, E Terwilliger, A Dayton, C Rosen, W Haseltine, and J Sodroski

The envelope of the human immunodeficiency virus type 1 (HIV-1) plays a central role in the process of virus entry into the host cell and in the cytopathicity of the virus for lymphocytes bearing the CD4 molecule. Mutations that affect the ability of the envelope glycoprotein to form syncytia in CD4+ cells can be divided into five groups: those that decrease the binding of the envelope protein to the CD4 molecule, those that prevent a post-binding fusion reaction, those that disrupt the anchorage of the envelope glycoprotein in the membrane, those that affect the association of the two subunits of the envelope glycoprotein, and those that affect post-translational proteolytic processing of the envelope precursor protein. These findings provide a functional model of the HIV envelope glycoprotein.


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Predicting proteolytic sites in extracellular proteins: only halfway there.
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Small molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion.
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Resistance to enfuvirtide, the first HIV fusion inhibitor.
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F. Diaz-Griffero, S. A. Hoschander, and J. Brojatsch (2003)
J. Virol. 77, 12552-12561
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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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Caprine Arthritis-Encephalitis Virus Envelope Surface Glycoprotein Regions Interacting with the Transmembrane Glycoprotein: Structural and Functional Parallels with Human Immunodeficiency Virus Type 1 gp120.
I. Hotzel and W. P. Cheevers (2003)
J. Virol. 77, 11578-11587
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S. G. Peisajovich, S. A. Gallo, R. Blumenthal, and Y. Shai (2003)
J. Biol. Chem. 278, 21012-21017
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Novel Therapies Based on Mechanisms of HIV-1 Cell Entry.
J. M. Kilby and J. J. Eron (2003)
N. Engl. J. Med. 348, 2228-2238
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J. J. Kohler, D. L. Tuttle, C. R. Coberley, J. W. Sleasman, and M. M. Goodenow (2003)
J. Leukoc. Biol. 73, 407-416
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Concordant Modulation of Neutralization Resistance and High Infectivity of the Primary Human Immunodeficiency Virus Type 1 MN Strain and Definition of a Potential gp41 Binding Site in gp120.
M. Leavitt, E. J. Park, I. A. Sidorov, D. S. Dimitrov, and G. V. Quinnan Jr. (2002)
J. Virol. 77, 560-570
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Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120.
R. Pantophlet, E. Ollmann Saphire, P. Poignard, P. W. H. I. Parren, I. A. Wilson, and D. R. Burton (2002)
J. Virol. 77, 642-658
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Membrane Structure of the Human Immunodeficiency Virus gp41 Fusion Domain by Molecular Dynamics Simulation.
S. Kamath and T. C. Wong (2002)
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Effect of Point Mutations in the N Terminus of the Lentivirus Lytic Peptide-1 Sequence of Human Immunodeficiency Virus Type 1 Transmembrane Protein gp41 on Env Stability.
S.-F. Lee, C.-Y. Ko, C.-T. Wang, and S. S.-L. Chen (2002)
J. Biol. Chem. 277, 15363-15375
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Role of N-Linked Glycans in a Human Immunodeficiency Virus Envelope Glycoprotein: Effects on Protein Function and the Neutralizing Antibody Response.
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J. Virol. 75, 9601-9612
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Effect of Soluble CD4 on Exposure of Epitopes on Primary, Intact, Native Human Immunodeficiency Virus Type 1 Virions of Different Genetic Clades.
H. A. Mbah, S. Burda, M. K. Gorny, C. Williams, K. Revesz, S. Zolla-Pazner, and P. N. Nyambi (2001)
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Mutational Analysis of Conserved Domains within the Cytoplasmic Tail of gp41 from Human Immunodeficiency Virus Type 1: Effects on Glycoprotein Incorporation and Infectivity.
S. C. Piller, J. W. Dubay, C. A. Derdeyn, and E. Hunter (2000)
J. Virol. 74, 11717-11723
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Modifications That Stabilize Human Immunodeficiency Virus Envelope Glycoprotein Trimers in Solution.
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Envelope Glycoprotein Determinants of Increased Fusogenicity in a Pathogenic Simian-Human Immunodeficiency Virus (SHIV-KB9) Passaged In Vivo.
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J. Virol. 74, 4433-4440
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The SU and TM Envelope Protein Subunits of Bovine Leukemia Virus Are Linked by Disulfide Bonds, both in Cells and in Virions.
E. R. Johnston and K. Radke (2000)
J. Virol. 74, 2930-2935
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Characterization of the Sequence of Interactions of the Fusion Domain of the Simian Immunodeficiency Virus with Membranes. ROLE OF THE MEMBRANE DIPOLE POTENTIAL.
J. Cladera, I. Martin, J.-M. Ruysschaert, and P. O'Shea (1999)
J. Biol. Chem. 274, 29951-29959
   Abstract »    Full Text »    PDF »
trans-Dominant Interference with Human Immunodeficiency Virus Type 1 Replication and Transmission in CD4+ Cells by an Envelope Double Mutant.
S. S.-L. Chen, S.-F. Lee, C.-K. Chuang, and V. S. Raj (1999)
J. Virol. 73, 8290-8302
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Determinants of Neutralization Resistance in the Envelope Glycoproteins of a Simian-Human Immunodeficiency Virus Passaged In Vivo.
B. Etemad-Moghadam, Y. Sun, E. K. Nicholson, G. B. Karlsson, D. Schenten, and J. Sodroski (1999)
J. Virol. 73, 8873-8879
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Cross-Subtype Neutralizing Antibodies Induced in Baboons by a Subtype E gp120 Immunogen Based on an R5 Primary Human Immunodeficiency Virus Type 1 Envelope.
T. C. VanCott, J. R. Mascola, L. D. Loomis-Price, F. Sinangil, N. Zitomersky, J. McNeil, M. L. Robb, D. L. Birx, and S. Barnett (1999)
J. Virol. 73, 4640-4650
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T20/DP178, an Ectodomain Peptide of Human Immunodeficiency Virus Type 1 gp41, Is an Activator of Human Phagocyte N-Formyl Peptide Receptor.
S. B. Su, W.-h. Gong, J.-L. Gao, W.-P. Shen, M. C. Grimm, X. Deng, P. M. Murphy, J. J. Oppenheim, and J. M. Wang (1999)
Blood 93, 3885-3892
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T21/DP107, A Synthetic Leucine Zipper-Like Domain of the HIV-1 Envelope gp41, Attracts and Activates Human Phagocytes by Using G-Protein-Coupled Formyl Peptide Receptors.
S. B. Su, J.-l. Gao, W.-h. Gong, N. M. Dunlop, P. M. Murphy, J. J. Oppenheim, and J. M. Wang (1999)
J. Immunol. 162, 5924-5930
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Complete Sequence of Enzootic Nasal Tumor Virus, a Retrovirus Associated with Transmissible Intranasal Tumors of Sheep.
C. Cousens, E. Minguijon, R. G. Dalziel, A. Ortin, M. Garcia, J. Park, L. Gonzalez, J. M. Sharp, and M. de las Heras (1999)
J. Virol. 73, 3986-3993
   Abstract »    Full Text »
Biophysical Characterization of the Structure of the Amino-terminal Region of gp41 of HIV-1. IMPLICATIONS ON VIRAL FUSION MECHANISM.
D.-K. Chang, S.-F. Cheng, and V. D. Trivedi (1999)
J. Biol. Chem. 274, 5299-5309
   Abstract »    Full Text »    PDF »
The YXXL Sequences of a Transmembrane Protein of Bovine Leukemia Virus Are Required for Viral Entry and Incorporation of Viral Envelope Protein into Virions.
K. Inabe, M. Nishizawa, S. Tajima, K. Ikuta, and Y. Aida (1999)
J. Virol. 73, 1293-1301
   Abstract »    Full Text »
HIV-induced T-cell syncytia release a two component T-helper cell chemoattractant composed of Nef and Tat.
D. Shutt and D. Soll (1999)
J. Cell Sci. 112, 3931-3941
   Abstract »    PDF »
Characterization of Simian-Human Immunodeficiency Virus Envelope Glycoprotein Epitopes Recognized by Neutralizing Antibodies from Infected Monkeys.
B. Etemad-Moghadam, G. B. Karlsson, M. Halloran, Y. Sun, D. Schenten, M. Fernandes, N. L. Letvin, and J. Sodroski (1998)
J. Virol. 72, 8437-8445
   Abstract »    Full Text »    PDF »
Identification of an Erythrocyte Binding Peptide from the Erythrocyte Binding Antigen, EBA-175, Which Blocks Parasite Multiplication and Induces Peptide-Blocking Antibodies.
P. H. Jakobsen, P. M. H. Heegaard, C. Koch, K. Wasniowska, M. M. Lemnge, J. B. Jensen, and B. K. L. Sim (1998)
Infect. Immun. 66, 4203-4207
   Abstract »    Full Text »    PDF »
Dissociation of the CD4 and CXCR4 Binding Properties of Human Immunodeficiency Virus Type 1 gp120 by Deletion of the First Putative Alpha-Helical Conserved Structure.
D. Misse, M. Cerutti, I. Schmidt, A. Jansen, G. Devauchelle, F. Jansen, and F. Veas (1998)
J. Virol. 72, 7280-7288
   Abstract »    Full Text »    PDF »
Stabilization of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers by Disulfide Bonds Introduced into the gp41 Glycoprotein Ectodomain.
M. Farzan, H. Choe, E. Desjardins, Y. Sun, J. Kuhn, J. Cao, D. Archambault, P. Kolchinsky, M. Koch, R. Wyatt, et al. (1998)
J. Virol. 72, 7620-7625
   Abstract »    Full Text »    PDF »
Determinants of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Activation by Soluble CD4 and Monoclonal Antibodies.
N. Sullivan, Y. Sun, J. Binley, J. Lee, C. F. Barbas III, P. W. H. I. Parren, D. R. Burton, and J. Sodroski (1998)
J. Virol. 72, 6332-6338
   Abstract »    Full Text »    PDF »
Expression of the Extracellular Domain of the Human Immunodeficiency Virus Type 1 Envelope Protein and Its Fusion with beta -Galactosidase in Saccharomyces cerevisiae.
W.-F. Liu, D. Gao, and Z.-N. Wang (1998)
Clin. Vaccine Immunol. 5, 592-594
   Abstract »    Full Text »
Functional Domains in the Retroviral Transmembrane Protein.
Y. Zhao, L. Zhu, C. A. Benedict, D. Chen, W. F. Anderson, and P. M. Cannon (1998)
J. Virol. 72, 5392-5398
   Abstract »    Full Text »    PDF »
A synthetic all D-amino acid peptide corresponding to the N-terminal sequence of HIV-1 gp41 recognizes the wild-type fusion peptide in the membrane and inhibits HIV-1 envelope glycoprotein-mediated cell fusion.
M. Pritsker, P. Jones, R. Blumenthal, and Y. Shai (1998)
PNAS 95, 7287-7292
   Abstract »    Full Text »    PDF »
The HIV-1 Envelope Glycoproteins: Fusogens, Antigens, and Immunogens.
R. Wyatt and J. Sodroski (1998)
Science 280, 1884-1888
   Abstract »    Full Text »
Mutation-Directed Chemical Cross-Linking of Human Immunodeficiency Virus Type 1 gp41 Oligomers.
T. L. McInerney, W. El Ahmar, B. E. Kemp, and P. Poumbourios (1998)
J. Virol. 72, 1523-1533
   Abstract »    Full Text »    PDF »
Mutational Analysis of the Fusion Peptide of Moloney Murine Leukemia Virus Transmembrane Protein p15E.
N.-L. Zhu, P. M. Cannon, D. Chen, and W. F. Anderson (1998)
J. Virol. 72, 1632-1639
   Abstract »    Full Text »    PDF »
Use of Murine CXCR-4 as a Second Receptor by Some T-Cell-Tropic Human Immunodeficiency Viruses.
C. Parolin, A. Borsetti, H. Choe, M. Farzan, P. Kolchinsky, M. Heesen, Q. Ma, C. Gerard, G. Palu, M. E. Dorf, et al. (1998)
J. Virol. 72, 1652-1656
   Abstract »    Full Text »    PDF »
Dilation of the Human Immunodeficiency Virus-1 Envelope Glycoprotein Fusion Pore Revealed by the Inhibitory Action of a Synthetic Peptide from gp41.
I. Munoz-Barroso, S. Durell, K. Sakaguchi, E. Appella, and R. Blumenthal (1998)
J. Cell Biol. 140, 315-323
   Abstract »    Full Text »    PDF »
Identification of a CD36-related Thrombospondin 1-binding Domain in HIV-1 Envelope Glycoprotein gp120: Relationship to HIV-1-specific Inhibitory Factors in Human Saliva.
R. Crombie, R. L. Silverstein, C. MacLow, S. F. A. Pearce, R. L. Nachman, and J. Laurence (1998)
J. Exp. Med. 187, 25-35
   Abstract »    Full Text »    PDF »
T cell syncytia induced by HIV release. T cell chemoattractants: demonstration with a newly developed single cell chemotaxis chamber.
D. Shutt, L. Jenkins, E. Carolan, J Stapleton, K. Daniels, R. Kennedy, and D. Soll (1998)
J. Cell Sci. 111, 99-109
   Abstract »    PDF »
CD4-Independent Binding of SIV gp120 to Rhesus CCR5.
K. A. Martin, R. Wyatt, M. Farzan, H. Choe, L. Marcon, E. Desjardins, J. Robinson, J. Sodroski, C. Gerard, and N. P. Gerard (1997)
Science 278, 1470-1473
   Abstract »    Full Text »
Two Orphan Seven-Transmembrane Segment Receptors Which Are Expressed in CD4-positive Cells Support Simian Immunodeficiency Virus Infection.
M. Farzan, H. Choe, K. Martin, L. Marcon, W. Hofmann, G. Karlsson, Y. Sun, P. Barrett, N. Marchand, N. Sullivan, et al. (1997)
J. Exp. Med. 186, 405-411
   Abstract »    Full Text »    PDF »
Assembly of a rod-shaped chimera of a trimeric GCN4 zipper and the HIV-1 gp41 ectodomain expressed in Escherichia coli.
W. Weissenhorn, L. J. Calder, A. Dessen, T. Laue, J. J. Skehel, and D. C. Wiley (1997)
PNAS 94, 6065-6069
   Abstract »    Full Text »    PDF »
Identification of the Paired Basic Convertases Implicated in HIV gp160 Processing Based on in Vitro Assays and Expression in CD4+ Cell Lines.
E. Decroly, S. Wouters, C. Di Bello, C. Lazure, J.-M. Ruysschaert, and N. G. Seidah (1996)
J. Biol. Chem. 271, 30442-30450
   Abstract »    Full Text »    PDF »
A Synthetic Conformational Epitope from the C4 Domain of HIV Gp120 That Binds CD4.
F. A. Robey, T. Harris-Kelson, M. Robert-Guroff, B. Ivanov, M. S. Lewis, and P. P. Roller (1996)
J. Biol. Chem. 271, 17990-17995
   Abstract »    Full Text »    PDF »
The Role of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in Virus Infection.
E. O. Freed and M. A. Martin (1995)
J. Biol. Chem. 270, 23883-23886
   Full Text »    PDF »
A Helical Epitope in the C4 Domain of HIV Glycoprotein 120.
F. A. Robey, T. Kelson-Harris, P. P. Roller, and M. Robert-Guroff (1995)
J. Biol. Chem. 270, 23918-23921
   Abstract »    Full Text »    PDF »
Biochemical and Genetic Definition of the Cellular Protease Required for HIV-1 gp160 Processing.
A. Franzusoff, A. M. Volpe, D. Josse, S. Pichuantes, and J. R. Wolf (1995)
J. Biol. Chem. 270, 3154-3159
   Abstract »    Full Text »    PDF »
Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide.
J. Harouse, S Bhat, S. Spitalnik, M Laughlin, K Stefano, D. Silberberg, and F Gonzalez-Scarano (1991)
Science 253, 320-323
   Abstract »    PDF »
Dissociation of gp120 from HIV-1 virions induced by soluble CD4.
J. Moore, J. McKeating, R. Weiss, and Q. Sattentau (1990)
Science 250, 1139-1142
   Abstract »    PDF »
Functional analysis of CAR, the target sequence for the Rev protein of HIV-1.
E. Dayton, D. Powell, and A. Dayton (1989)
Science 246, 1625-1629
   Abstract »    PDF »
Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation.
J. Hildreth and R. Orentas (1989)
Science 244, 1075-1078
   Abstract »    PDF »
Identification of the fusion peptide of primate immunodeficiency viruses.
M. Bosch, P. Earl, K Fargnoli, S Picciafuoco, F Giombini, F Wong-Staal, and G Franchini (1989)
Science 244, 694-697
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Synthetic CD4 peptide derivatives that inhibit HIV infection and cytopathicity.
J. Lifson, K. Hwang, P. Nara, B Fraser, M Padgett, N. Dunlop, and L. Eiden (1988)
Science 241, 712-716
   Abstract »    PDF »
Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein.
B. Jameson, P. Rao, L. Kong, B. Hahn, G. Shaw, L. Hood, and S. Kent (1988)
Science 240, 1335-1339
   Abstract »    PDF »
Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells.
H Mitsuya, D. Looney, S Kuno, R Ueno, F Wong-Staal, and S Broder (1988)
Science 240, 646-649
   Abstract »    PDF »
Second conserved domain of gp120 is important for HIV infectivity and antibody neutralization.
D. Ho, J. Kaplan, I. Rackauskas, and M. Gurney (1988)
Science 239, 1021-1023
   Abstract »    PDF »
Multimerization Potential of the Cytoplasmic Domain of the Human Immunodeficiency Virus Type 1 Transmembrane Glycoprotein gp41.
S.-F. Lee, C.-T. Wang, J. Y.-P. Liang, S.-L. Hong, C.-C. Huang, and S. S.-L. Chen (2000)
J. Biol. Chem. 275, 15809-15819
   Abstract »    Full Text »    PDF »
Mode of Action of an Antiviral Peptide from HIV-1. INHIBITION AT A POST-LIPID MIXING STAGE.
Y. Kliger, S. A. Gallo, S. G. Peisajovich, I. Munoz-Barroso, S. Avkin, R. Blumenthal, and Y. Shai (2001)
J. Biol. Chem. 276, 1391-1397
   Abstract »    Full Text »    PDF »
Early Intermediates in HIV-1 Envelope Glycoprotein-mediated Fusion Triggered by CD4 and Co-receptor Complexes.
A. S. Dimitrov, X. Xiao, D. S. Dimitrov, and R. Blumenthal (2001)
J. Biol. Chem. 276, 30335-30341
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