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Science 28 June 1996:
Vol. 272. no. 5270, pp. 1955 - 1958
DOI: 10.1126/science.272.5270.1955
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Reports

CC CKR5: A RANTES, MIP-1alpha , MIP-1beta Receptor as a Fusion Cofactor for Macrophage-Tropic HIV-1

Ghalib Alkhatib, Christophe Combadiere, * Christopher C. Broder, * Yu Feng, * Paul E. Kennedy, * Philip M. Murphy, dagger Edward A. Berger dagger

Human immunodeficiency virus-type 1 (HIV-1) entry requires fusion cofactors on the CD4+ target cell. Fusin, a heterotrimeric GTP-binding protein (G protein)-coupled receptor, serves as a cofactor for T cell line-tropic isolates. The chemokines RANTES, MIP-1alpha , and MIP-1beta , which suppress infection by macrophage-tropic isolates, selectively inhibited cell fusion mediated by the corresponding envelope glycoproteins (Envs). Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs. CC CKR5 messenger RNA was detected selectively in cell types susceptible to macrophage-tropic isolates. CC CKR5 is thus a fusion cofactor for macrophage-tropic HIV-1 strains.

G. Alkhatib, C. C. Broder, Y. Feng, P. E. Kennedy, E. A. Berger, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA
C. Combadiere and P. M. Murphy, Laboratory of Host Defenses, NIAID, NIH, Bethesda, MD 20892, USA.
* These authors contributed equally to the research.
dagger To whom correspondence should be addressed.


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B. L. Walter, K. Wehrly, R. Swanstrom, E. Platt, D. Kabat, and B. Chesebro (2005)
J. Virol. 79, 4828-4837
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Variants of Human Immunodeficiency Virus Type 1 That Efficiently Use CCR5 Lacking the Tyrosine-Sulfated Amino Terminus Have Adaptive Mutations in gp120, Including Loss of a Functional N-Glycan.
E. J. Platt, D. M. Shea, P. P. Rose, and D. Kabat (2005)
J. Virol. 79, 4357-4368
   Abstract »    Full Text »    PDF »
The CCR5 Receptor-Based Mechanism of Action of 873140, a Potent Allosteric Noncompetitive HIV Entry Inhibitor.
C. Watson, S. Jenkinson, W. Kazmierski, and T. Kenakin (2005)
Mol. Pharmacol. 67, 1268-1282
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Reappraisal of the historical selective pressures for the CCR5-{Delta}32 mutation.
S R Duncan, S Scott, and C J Duncan (2005)
J. Med. Genet. 42, 205-208
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Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design.
R. Varadarajan, D. Sharma, K. Chakraborty, M. Patel, M. Citron, P. Sinha, R. Yadav, U. Rashid, S. Kennedy, D. Eckert, et al. (2005)
J. Virol. 79, 1713-1723
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Structural Determinants of the Anti-HIV Activity of a CCR5 Antagonist Derived from Toxoplasma gondii.
F. Yarovinsky, J. F. Andersen, L. R. King, P. Caspar, J. Aliberti, H. Golding, and A. Sher (2004)
J. Biol. Chem. 279, 53635-53642
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Inhibition of Human Immunodeficiency Virus Replication by a Dual CCR5/CXCR4 Antagonist.
K. Princen, S. Hatse, K. Vermeire, S. Aquaro, E. De Clercq, L.-O. Gerlach, M. Rosenkilde, T. W. Schwartz, R. Skerlj, G. Bridger, et al. (2004)
J. Virol. 78, 12996-13006
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Coevolution of RANTES Sensitivity and Mode of CCR5 Receptor Use by Human Immunodeficiency Virus Type 1 of the R5 Phenotype.
I. Karlsson, L. Antonsson, Y. Shi, M. Oberg, A. Karlsson, J. Albert, B. Olde, C. Owman, M. Jansson, and E. M. Fenyo (2004)
J. Virol. 78, 11807-11815
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Recall antigen activation induces prompt release of CCR5 ligands from PBMC: implication in memory responses and immunization.
L. Sun, S. F. Abdelwahab, G. K. Lewis, and A. Garzino-Demo (2004)
Int. Immunol. 16, 1623-1631
   Abstract »    Full Text »    PDF »
Inhibition of human immunodeficiency virus type 1 replication by Z-100, an immunomodulator extracted from human-type tubercle bacilli, in macrophages.
Y. Emori, T. Ikeda, T. Ohashi, T. Masuda, T. Kurimoto, M. Takei, and M. Kannagi (2004)
J. Gen. Virol. 85, 2603-2613
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R5 Human Immunodeficiency Virus Type 1 (HIV-1) Replicates More Efficiently in Primary CD4+ T-Cell Cultures Than X4 HIV-1.
B. Schweighardt, A.-M. Roy, D. A. Meiklejohn, E. J. Grace II, W. J. Moretto, J. J. Heymann, and D. F. Nixon (2004)
J. Virol. 78, 9164-9173
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Detection of a Short CCR5 Messenger RNA Isoform in Human Spermatozoa.
R. Januchowski, A. K. Breborowicz, H. Ofori, P. Jedrzejczak, L. Pawelczyk, and P. P. Jagodzinski (2004)
J Androl 25, 757-760
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I-TAC/CXCL11 is a natural antagonist for CCR5.
V. Petkovic, C. Moghini, S. Paoletti, M. Uguccioni, and B. Gerber (2004)
J. Leukoc. Biol. 76, 701-708
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THE BURDEN OF CO-INFECTION WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 AND MALARIA IN PREGNANT WOMEN IN SUB-SAHARAN AFRICA.
F. O. TER KUILE, M. E. PARISE, F. H. VERHOEFF, V. UDHAYAKUMAR, R. D. NEWMAN, A. M. VAN EIJK, S. J. ROGERSON, and R. W. STEKETEE (2004)
Am J Trop Med Hyg 71, 41-54
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Characterization of the Conformational State and Flexibility of HIV-1 Glycoprotein gp120 Core Domain.
Y. Pan, B. Ma, O. Keskin, and R. Nussinov (2004)
J. Biol. Chem. 279, 30523-30530
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Intrinsic Obstacles to Human Immunodeficiency Virus Type 1 Coreceptor Switching.
C. Pastore, A. Ramos, and D. E. Mosier (2004)
J. Virol. 78, 7565-7574
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CD4-Induced T-20 Binding to Human Immunodeficiency Virus Type 1 gp120 Blocks Interaction with the CXCR4 Coreceptor.
W. Yuan, S. Craig, Z. Si, M. Farzan, and J. Sodroski (2004)
J. Virol. 78, 5448-5457
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Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages.
Y. Hoshino, D. B. Tse, G. Rochford, S. Prabhakar, S. Hoshino, N. Chitkara, K. Kuwabara, E. Ching, B. Raju, J. A. Gold, et al. (2004)
J. Immunol. 172, 6251-6258
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Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection.
Z.-Q. Zhang, S. W. Wietgrefe, Q. Li, M. D. Shore, L. Duan, C. Reilly, J. D. Lifson, and A. T. Haase (2004)
PNAS 101, 5640-5645
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N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies.
R. A. McCaffrey, C. Saunders, M. Hensel, and L. Stamatatos (2004)
J. Virol. 78, 3279-3295
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A syndecan-4/CXCR4 complex expressed on human primary lymphocytes and macrophages and HeLa cell line binds the CXC chemokine stromal cell-derived factor-1 (SDF-1).
M. Hamon, E. Mbemba, N. Charnaux, H. Slimani, S. Brule, L. Saffar, R. Vassy, C. Prost, N. Lievre, A. Starzec, et al. (2004)
Glycobiology 14, 311-323
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Patterns of ethnic diversity among the genes that influence AIDS.
C. Winkler, P. An, and S. J. O'Brien (2004)
Hum. Mol. Genet. 13, R9-19
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In Vivo Evolution of X4 Human Immunodeficiency Virus Type 1 Variants in the Natural Course of Infection Coincides with Decreasing Sensitivity to CXCR4 Antagonists.
E. H. B. Stalmeijer, R. P. van Rij, B. Boeser-Nunnink, J. A. Visser, M. A. Naarding, D. Schols, and H. Schuitemaker (2004)
J. Virol. 78, 2722-2728
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Role for CCR5{Delta}32 Protein in Resistance to R5, R5X4, and X4 Human Immunodeficiency Virus Type 1 in Primary CD4+ Cells.
L. Agrawal, X. Lu, J. Qingwen, Z. VanHorn-Ali, I. V. Nicolescu, D. H. McDermott, P. M. Murphy, and G. Alkhatib (2004)
J. Virol. 78, 2277-2287
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