Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding

doi:10.1084/jem.172.4.1233

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Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding

D Healey, L Dianda, JP Moore, JS McDougal, MJ Moore, P Estess, D Buck, PD Kwong, PC Beverley and QJ Sattentau
Academic Department of Genito-Urinary Medicine, University College and Middlesex School of Medicine, London.

Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.
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Ashish, , Juncadella, I. J., Garg, R., Boone, C. D., Anguita, J., Krueger, J. K. (2008). Conformational Rearrangement within the Soluble Domains of the CD4 Receptor Is Ligand-specific. J. Biol. Chem. 283: 2761-2772 [Abstract] [Full Text]
Yang, X., Lipchina, I., Lifton, M., Wang, L., Sodroski, J. (2007). Antibody Binding in Proximity to the Receptor/Glycoprotein Complex Leads to a Basal Level of Virus Neutralization. J. Virol. 81: 8809-8813 [Abstract] [Full Text]
Jolly, C., Mitar, I., Sattentau, Q. J. (2007). Requirement for an Intact T-Cell Actin and Tubulin Cytoskeleton for Efficient Assembly and Spread of Human Immunodeficiency Virus Type 1. J. Virol. 81: 5547-5560 [Abstract] [Full Text]
Byland, R., Vance, P. J., Hoxie, J. A., Marsh, M. (2007). A Conserved Dileucine Motif Mediates Clathrin and AP-2-dependent Endocytosis of the HIV-1 Envelope Protein. Mol. Biol. Cell 18: 414-425 [Abstract] [Full Text]
Zhou, T., Hamer, D. H., Hendrickson, W. A., Sattentau, Q. J., Kwong, P. D. (2005). Interfacial metal and antibody recognition. Proc. Natl. Acad. Sci. USA 102: 14575-14580 [Abstract] [Full Text]
Blanco, J., Bosch, B., Fernandez-Figueras, M. T., Barretina, J., Clotet, B., Este, J. A. (2004). High Level of Coreceptor-independent HIV Transfer Induced by Contacts between Primary CD4 T Cells. J. Biol. Chem. 279: 51305-51314 [Abstract] [Full Text]
Blanco, J., Barretina, J., Clotet, B., Este, J. A. (2004). R5 HIV gp120-mediated cellular contacts induce the death of single CCR5-expressing CD4 T cells by a gp41-dependent mechanism. J. Leukoc. Biol. 76: 804-811 [Abstract] [Full Text]
Jolly, C., Kashefi, K., Hollinshead, M., Sattentau, Q. J. (2004). HIV-1 Cell to Cell Transfer across an Env-induced, Actin-dependent Synapse. JEM 199: 283-293 [Abstract] [Full Text]
Burrer, R., Haessig-Einius, S., Aubertin, A.-M., Moog, C. (2003). Polyclonal Immunoglobulin G from Patients Neutralizes Human Immunodeficiency Virus Type 1 Primary Isolates by Binding Free Virions, but without Interfering with an Initial CD4-Independent Attachment of the Virus to Primary Blood Mononuclear Cells. J. Virol. 77: 11385-11397 [Abstract] [Full Text]
Willey, S. J., Reeves, J. D., Hudson, R., Miyake, K., Dejucq, N., Schols, D., Clercq, E. D., Bell, J., McKnight, A., Clapham, P. R. (2003). Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells. J. Virol. 77: 6138-6152 [Abstract] [Full Text]
Percherancier, Y., Lagane, B., Planchenault, T., Staropoli, I., Altmeyer, R., Virelizier, J.-L., Arenzana-Seisdedos, F., Hoessli, D. C., Bachelerie, F. (2003). HIV-1 Entry into T-cells Is Not Dependent on CD4 and CCR5 Localization to Sphingolipid-enriched, Detergent-resistant, Raft Membrane Domains. J. Biol. Chem. 278: 3153-3161 [Abstract] [Full Text]
Fouts, T., Godfrey, K., Bobb, K., Montefiori, D., Hanson, C. V., Kalyanaraman, V. S., DeVico, A., Pal, R. (2002). Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques. Proc. Natl. Acad. Sci. USA 99: 11842-11847 [Abstract] [Full Text]
Clapham, P. R., McKnight, A. (2002). Cell surface receptors, virus entry and tropism of primate lentiviruses. J. Gen. Virol. 83: 1809-1829 [Abstract] [Full Text]
Golding, H., Zaitseva, M., de Rosny, E., King, L. R., Manischewitz, J., Sidorov, I., Gorny, M. K., Zolla-Pazner, S., Dimitrov, D. S., Weiss, C. D. (2002). Dissection of Human Immunodeficiency Virus Type 1 Entry with Neutralizing Antibodies to gp41 Fusion Intermediates. J. Virol. 76: 6780-6790 [Abstract] [Full Text]
Guillon, C., Schutten, M., Boers, P. H. M., Gruters, R. A., Osterhaus, A. D. M. E. (2002). Antibody-Mediated Enhancement of Human Immunodeficiency Virus Type 1 Infectivity Is Determined by the Structure of gp120 and Depends on Modulation of the gp120-CCR5 Interaction. J. Virol. 76: 2827-2834 [Abstract] [Full Text]
Fraile-Ramos, A., Kledal, T. N., Pelchen-Matthews, A., Bowers, K., Schwartz, T. W., Marsh, M. (2001). The Human Cytomegalovirus US28 Protein Is Located in Endocytic Vesicles and Undergoes Constitutive Endocytosis and Recycling. Mol. Biol. Cell 12: 1737-1749 [Abstract] [Full Text]
Genois, N., Robichaud, G. A, Tremblay, M. J. (2000). Mono Mac 1: a new in vitro model system to study HIV-1 infection in human cells of the mononuclear phagocyte series. J. Leukoc. Biol. 68: 854-864 [Abstract] [Full Text]
Melikyan, G. B., Markosyan, R. M., Hemmati, H., Delmedico, M. K., Lambert, D. M., Cohen, F. S. (2000). Evidence That the Transition of HIV-1 gp41 into a Six-Helix Bundle, Not the Bundle Configuration, Induces Membrane Fusion. JCB 151: 413-424 [Abstract] [Full Text]
Moulard, M., Lortat-Jacob, H., Mondor, I., Roca, G., Wyatt, R., Sodroski, J., Zhao, L., Olson, W., Kwong, P. D., Sattentau, Q. J. (2000). Selective Interactions of Polyanions with Basic Surfaces on Human Immunodeficiency Virus Type 1 gp120. J. Virol. 74: 1948-1960 [Abstract] [Full Text]
Klasse, P. J., Rosenkilde, M. M., Signoret, N., Pelchen-Matthews, A., Schwartz, T. W., Marsh, M. (1999). CD4-Chemokine Receptor Hybrids in Human Immunodeficiency Virus Type 1 Infection. J. Virol. 73: 7453-7466 [Abstract] [Full Text]
Reeves, J. D., Hibbitts, S., Simmons, G., McKnight, A., Azevedo-Pereira, J. M., Moniz-Pereira, J., Clapham, P. R. (1999). Primary Human Immunodeficiency Virus Type 2 (HIV-2) Isolates Infect CD4-Negative Cells via CCR5 and CXCR4: Comparison with HIV-1 and Simian Immunodeficiency Virus and Relevance to Cell Tropism In Vivo. J. Virol. 73: 7795-7804 [Abstract] [Full Text]
Lee, B., Sharron, M., Montaner, L. J., Weissman, D., Doms, R. W. (1999). Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc. Natl. Acad. Sci. USA 96: 5215-5220 [Abstract] [Full Text]
HOWIE, S. E. M., FERNANDES, M. L., HESLOP, I., HEWSON, T. J., COTTON, G. J., MOORE, M. J., INNES, D., RAMAGE, R., HARRISON, D. J. (1999). A functional, discontinuous HIV-1 gp120 C3/C4 domain-derived, branched, synthetic peptide that binds to CD4 and inhibits MIP-1{alpha} chemokine binding. FASEB J. 13: 503-511 [Abstract] [Full Text]
Pitcher, C., Höning, S., Fingerhut, A., Bowers, K., Marsh, M. (1999). Cluster of Differentiation Antigen 4�() Endocytosis and Adaptor Complex Binding Require Activation of the Endocytosis Signal by Serine Phosphorylation. Mol. Biol. Cell 10: 677-691 [Abstract] [Full Text]
Jackson, N., Levi, M, Wahren, B, Dimmock, N. (1999). Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions. J. Gen. Virol. 80: 225-236 [Abstract]
Mondor, I., Ugolini, S., Sattentau, Q. J. (1998). Human Immunodeficiency Virus Type 1�Attachment to HeLa CD4 Cells Is CD4 Independent and gp120 Dependent and Requires Cell Surface Heparans. J. Virol. 72: 3623-3634 [Abstract] [Full Text]
Signoret, N, Rosenkilde, M., Klasse, P., Schwartz, T., Malim, M., Hoxie, J., Marsh, M (1998). Differential regulation of CXCR4 and CCR5 endocytosis. J. Cell Sci. 111: 2819-2830 [Abstract]
Signoret, N., Oldridge, J., Pelchen-Matthews, A., Klasse, P. J., Tran, T., Brass, L. F., Rosenkilde, M. M., Schwartz, T. W., Holmes, W., Dallas, W., Luther, M. A., Wells, T. N.C., Hoxie, J. A., Marsh, M. (1997). Phorbol Esters and SDF-1 Induce Rapid Endocytosis and Down Modulation of the Chemokine Receptor CXCR4. JCB 139: 651-664 [Abstract] [Full Text]
Ugolini, S., Mondor, I., Parren, P. W.H.I., Burton, D. R., Tilley, S. A., Klasse, P. J., Sattentau, Q. J. (1997). Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line-adapted HIV-1 Neutralization. JEM 186: 1287-1298 [Abstract] [Full Text]
Brady, R., Dodson, E., Dodson, G., Lange, G, Davis, S., Williams, A., Barclay, A. (1993). Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains. Science 260: 979-983 [Abstract]
Hendrickson, W.A., Kwong, P.D., Leahy, D.J., Ryu, S.-E., Yamaguchi, H., Fleury, S., Sekaly, R.-P. (1992). Structural Aspects of CD4 and CD8 Involvement in the Cellular Immune Response. Cold Spring Harb Symp Quant Biol 57: 549-556 [Abstract]
Moore, J., McKeating, J., Weiss, R., Sattentau, Q. (1990). Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science 250: 1139-1142 [Abstract]
Staropoli, I., Chanel, C., Girard, M., Altmeyer, R. (2000). Processing, Stability, and Receptor Binding Properties of Oligomeric Envelope Glycoprotein from a Primary HIV-1 Isolate. J. Biol. Chem. 275: 35137-35145 [Abstract] [Full Text]