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Science 13 December 1996:
Vol. 274. no. 5294, pp. 1924 - 1926
DOI: 10.1126/science.274.5294.1924
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Reports

Multiple Extracellular Elements of CCR5 and HIV-1 Entry: Dissociation from Response to Chemokines

Robert E. Atchison, * Jennifa Gosling, * Felipe S. Monteclaro, * Christian Franci, Laura Digilio, Israel F. Charo, Mark A. Goldsmith dagger

The human beta -chemokine receptor CCR5 is an important cofactor for entry of human immunodeficiency virus-type 1 (HIV-1). The murine form of CCR5, despite its 82 percent identity to the human form, was not functional as an HIV-1 coreceptor. HIV-1 entry function could be reconstituted by fusion of various individual elements derived from the extracellular region of human CCR5 onto murine CCR5. Analysis of chimeras containing elements from human CCR5 and human CCR2B suggested that a complex structure rather than single contact sites is responsible for facilitation of viral entry. Further, certain chimeras lacking the domains necessary to signal in response to their natural chemokine ligands retained vigorous HIV-1 coreceptor activity.

R. E. Atchison, L. Digilio, M. A. Goldsmith, Gladstone Institute of Virology and Immunology and Department of Medicine, School of Medicine, University of California, San Francisco, Post Office Box 419100, San Francisco, CA 94141-9100, USA.
J. Gosling, F. S. Monteclaro, C. Franci, I. F. Charo, Gladstone Institute of Cardiovascular Disease and Department of Medicine, School of Medicine, University of California, San Francisco, Post Office Box 419100, San Francisco, CA 94141-9100, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: mark_goldsmith{at}quickmail.ucsf.edu

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Z.-x. Wang, J. F. Berson, T.-y. Zhang, Y.-H. Cen, Y. Sun, M. Sharron, Z.-h. Lu, and S. C. Peiper (1998)
J. Biol. Chem. 273, 15007-15015
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Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1alpha , a potent ligand for the HIV-1 "fusin" coreceptor.
C. Dealwis, E. J. Fernandez, D. A. Thompson, R. J. Simon, M. A. Siani, and E. Lolis (1998)
PNAS 95, 6941-6946
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Entry of Amphotropic Murine Leukemia Virus Is Influenced by Residues in the Putative Second Extracellular Domain of Its Receptor, Pit2.
B. D. Leverett, K. B. Farrell, M. V. Eiden, and C. A. Wilson (1998)
J. Virol. 72, 4956-4961
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CCR5 coreceptor utilization involves a highly conserved arginine residue of HIV type 1 gp120.
W.-K. Wang, T. Dudek, Y.-J. Zhao, H. G. Brumblay, M. Essex, and T.-H. Lee (1998)
PNAS 95, 5740-5745
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The CCR5 receptor acts as an alloantigen in CCR5Delta 32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies.
H. J. Ditzel, M. M. Rosenkilde, P. Garred, M. Wang, K. Koefoed, C. Pedersen, D. R. Burton, and T. W. Schwartz (1998)
PNAS 95, 5241-5245
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Alanine Substitutions of Polar and Nonpolar Residues in the Amino-Terminal Domain of CCR5 Differently Impair Entry of Macrophage- and Dualtropic Isolates of Human Immunodeficiency Virus Type 1.
G. E. E. Rabut, J. A. Konner, F. Kajumo, J. P. Moore, and T. Dragic (1998)
J. Virol. 72, 3464-3468
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Evidence that Antibody-Mediated Neutralization of Human Immunodeficiency Virus Type 1 by Sera from Infected Individuals Is Independent of Coreceptor Usage.
D. C. Montefiori, R. G. Collman, T. R. Fouts, J. Y. Zhou, M. Bilska, J. A. Hoxie, J. P. Moore, and D. P. Bolognesi (1998)
J. Virol. 72, 1886-1893
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Multiple Residues Contribute to the Inability of Murine CCR-5 To Function as a Coreceptor for Macrophage-Tropic Human Immunodeficiency Virus Type 1 Isolates.
T. M. Ross, P. D. Bieniasz, and B. R. Cullen (1998)
J. Virol. 72, 1918-1924
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An Intricate Web: Chemokine Receptors, HIV-1 and Hematopoiesis.
B. Lee, B. J. Doranz, M. Z. Ratajczak, and R. W. Doms (1998)
Stem Cells 16, 79-88
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Genomic Organization and Functional Characterization of the Chemokine Receptor CXCR4, a Major Entry Co-receptor for Human Immunodeficiency Virus Type 1.
S. A. Wegner, P. K. Ehrenberg, G. Chang, D. E. Dayhoff, A. L. Sleeker, and N. L. Michael (1998)
J. Biol. Chem. 273, 4754-4760
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A Tyrosine-Rich Region in the N Terminus of CCR5 Is Important for Human Immunodeficiency Virus Type 1 Entry and Mediates an Association between gp120 and CCR5.
M. Farzan, H. Choe, L. Vaca, K. Martin, Y. Sun, E. Desjardins, N. Ruffing, L. Wu, R. Wyatt, N. Gerard, et al. (1998)
J. Virol. 72, 1160-1164
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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
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