HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 47, 39493-39504, November 25, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/47/39493    most recent M504233200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Parseval, A. Articles by Gallay, P. A. Search for Related Content PubMed PubMed Citation Articles by de Parseval, A. Articles by Gallay, P. A. Social Bookmarking                      What's this?

A Highly Conserved Arginine in gp120 Governs HIV-1 Binding to Both Syndecans and CCR5 via Sulfated Motifs^*

Aymeric de Parseval1, Michael D. Bobardt1, Anju Chatterji, Udayan Chatterji, John H. Elder, Guido David¶, Susan Zolla-Pazner||, Michael Farzan**, Tun-Hou Lee, and Philippe A. Gallay2

From the Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, the ^¶Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium, the ^||Department of Pathology, Institute of Environmental Medicine, New York University School of Medicine, New York, New York 10016, the ^**Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, and the Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115

HIV-1 has maximized its utilization of syndecans. It uses them as in cis receptors to infect macrophages and as in trans receptors to infect T-lymphocytes. In this study, we investigated at a molecular level the mechanisms that control HIV-1-syndecan interactions. We found that a single conserved arginine (Arg-298) in the V3 region of gp120 governs HIV-1 binding to syndecans. We found that an amine group on the side chain of this residue is necessary for syndecan utilization by HIV-1. Furthermore, we showed that HIV-1 binds syndecans via a 6-O sulfation, demonstrating that this binding is not the result of random interactions between basic residues and negative charges, but the result of specific contacts between gp120 and a well defined sulfation in syndecans. Surprisingly, we found that Arg-298, which mediates HIV-1 binding to syndecans, also mediates HIV-1 binding to CCR5. We postulated that HIV-1 recognizes similar motifs on syndecans and CCR5. Supporting this hypothesis, we obtained several lines of evidence that suggest that the 6-O sulfation recognized by HIV-1 on syndecans mimics the sulfated tyrosines recognized by HIV-1 in the N terminus of CCR5. Our finding that CCR5 and syndecans are exploited by HIV-1 via a single determinant echoes the mechanisms by which chemokines utilize these two disparate receptors and suggests that the gp120/chemokine mimicry may represent a common strategy in microbial pathogenesis.

Received for publication, April 19, 2005 , and in revised form, September 9, 2005.

^* This work was supported by U.S. Public Health Service Grant AI054196 (to P. A. G.). This is publication 16431-IMM from the Dept. of Immunology, The Scripps Research Institute, La Jolla, CA. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Dept. of Immunology IMM-9, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Tel.: 858-784-8180; Fax: 858-784-8227; E-mail: gallay{at}scripps.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Ghosh, K. Chattopadhyay, M. Marschall, P. Karmakar, P. Mandal, and B. Ray Focus on antivirally active sulfated polysaccharides: From structure-activity analysis to clinical evaluation Glycobiology, January 1, 2009; 19(1): 2 - 15. [Abstract] [Full Text] [PDF]

				E. Crublet, J.-P. Andrieu, R. R. Vives, and H. Lortat-Jacob The HIV-1 Envelope Glycoprotein gp120 Features Four Heparan Sulfate Binding Domains, Including the Co-receptor Binding Site J. Biol. Chem., May 30, 2008; 283(22): 15193 - 15200. [Abstract] [Full Text] [PDF]

				M. B. Patel, N. G. Hoffman, and R. Swanstrom Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins J. Virol., January 15, 2008; 82(2): 903 - 916. [Abstract] [Full Text] [PDF]

				L. de Witte, M. Bobardt, U. Chatterji, G. Degeest, G. David, T. B. H. Geijtenbeek, and P. Gallay Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1 PNAS, December 4, 2007; 104(49): 19464 - 19469. [Abstract] [Full Text] [PDF]

				E. Stoddard, G. Cannon, H. Ni, K. Kariko, J. Capodici, D. Malamud, and D. Weissman gp340 Expressed on Human Genital Epithelia Binds HIV-1 Envelope Protein and Facilitates Viral Transmission J. Immunol., September 1, 2007; 179(5): 3126 - 3132. [Abstract] [Full Text] [PDF]

				C. Pastore, R. Nedellec, A. Ramos, O. Hartley, J. L. Miamidian, J. D. Reeves, and D. E. Mosier Conserved Changes in Envelope Function during Human Immunodeficiency Virus Type 1 Coreceptor Switching J. Virol., August 1, 2007; 81(15): 8165 - 8179. [Abstract] [Full Text] [PDF]

				H. Saidi, G. Magri, C. Carbonneil, N. Nasreddine, M. Requena, and L. Belec IFN-{gamma}-activated monocytes weakly produce HIV-1 but induce the recruitment of HIV-sensitive T cells and enhance the viral production by these recruited T cells J. Leukoc. Biol., March 1, 2007; 81(3): 642 - 653. [Abstract] [Full Text] [PDF]

				M. D. Bobardt, U. Chatterji, S. Selvarajah, B. Van der Schueren, G. David, B. Kahn, and P. A. Gallay Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells J. Virol., January 1, 2007; 81(1): 395 - 405. [Abstract] [Full Text] [PDF]

				A. Sutton, V. Friand, S. Brule-Donneger, T. Chaigneau, M. Ziol, O. Sainte-Catherine, A. Poire, L. Saffar, M. Kraemer, J. Vassy, et al. Stromal Cell-Derived Factor-1/Chemokine (C-X-C Motif) Ligand 12 Stimulates Human Hepatoma Cell Growth, Migration, and Invasion Mol. Cancer Res., January 1, 2007; 5(1): 21 - 33. [Abstract] [Full Text] [PDF]

				S. M. Wahl, T. Greenwell-Wild, and N. Vazquez HIV accomplices and adversaries in macrophage infection J. Leukoc. Biol., November 1, 2006; 80(5): 973 - 983. [Abstract] [Full Text] [PDF]

				K. S. Jones, K. Fugo, C. Petrow-Sadowski, Y. Huang, D. C. Bertolette, I. Lisinski, S. W. Cushman, S. Jacobson, and F. W. Ruscetti Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Use Different Receptor Complexes To Enter T Cells. J. Virol., September 1, 2006; 80(17): 8291 - 8302. [Abstract] [Full Text] [PDF]