Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist

Journal of Virology

Volumn 78, Issue 23, 2004, Pages 12996-13006

  Princen, Katrien ^a   Hatse, Sigrid ^a   Vermeire, Kurt ^a   Aquaro, Stefano ^a,d   De Clercq, Erik ^a   Gerlach, Lars Ole ^b   Rosenkilde, Mette ^b   Schwartz, Thue W ^b   Skerlj, Renato ^c   Bridger, Gary ^c   Schols, Dominique ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c GENZYME CORPORATION   (United States)

^d UNIVERSITY OF ROME TOR VERGATA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1,1' [1,4 PHENYLENEBIS(METHYLENE)]BIS(1,4,8,11 TETRAAZACYCLOTETRADECANE); AMD 3451; CARBON TETRACHLORIDE; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; CYCLAM DERIVATIVE; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; ARTICLE; CALCIUM CELL LEVEL; CALCIUM SIGNALING; CALCIUM TRANSPORT; CELL ISOLATION; CELL LINE; CHEMOTAXIS; DRUG EFFICACY; DRUG SAFETY; ENDOCYTOSIS; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; IC 50; MACROPHAGE; MOLECULAR WEIGHT; MONOCYTE; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN INTERACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; T LYMPHOCYTE; VIRUS INHIBITION; VIRUS ISOLATION; VIRUS REPLICATION; VIRUS STRAIN;

ANTI-HIV AGENTS; ANTIBODIES, MONOCLONAL; CALCIUM; CHEMOKINES, CC; CHEMOKINES, CXC; CHEMOTAXIS; HETEROCYCLIC COMPOUNDS; HIV; HUMANS; PYRIDINES; RECEPTORS, CCR5; RECEPTORS, CXCR4; VIRUS REPLICATION;

EID: 8644270505     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.78.23.12996-13006.2004     Document Type: Article

References (65)

1. Alkhatib, G., C. Combadiere, C. C. Broder, Y. Feng, P. E. Kennedy, P. M. Murphy, and E. A. Berger. 1996. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272:1955-1958.
2. Aquaro, S., O. Wedgwood, C. Yarnold, D. Cahard, R. Pathinara, C. McGuigan, R. Calio, E. De Clercq, J. Balzarini, and C. F. Perno. 2000. Activities of masked 2′,3′-dideoxynucleoside monophosphate derivatives against human immunodeficiency virus in resting macrophages. Antimicrob. Agents Chemother. 44:173-177.
3. Arenzana-Seisdedos, F., J. L. Virelizier, D. Rousset, I. Clark-Lewis, P. Loetscher, B. Moser, and M. Baggiolini. 1996. HIV blocked by chemokine antagonist. Nature 383:400.
4. Baba, M., O. Nishimura, N. Kanzaki, M. Okamoto, H. Sawada, Y. Iizawa, M. Shiraishi, Y. Aramaki, K. Okonogi, Y. Ogawa, K. Meguro, and M. Fujino. 1999. A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. USA 96:5698-5703.
5. Baribaud, F., T. G. Edwards, M. Sharron, A. Brelot, N. Heveker, K. Price, F. Mortari, M. Alizon, M. Tsang, and R. W. Doms. 2001. Antigenically distinct conformations of CXCR4. J. Virol. 75:8957-8967.
6. Berger, E. A., P. M. Murphy, and J. M. Farber. 1999. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17:657-700.
7. Berson, J. F., D. Long, B. J. Doranz, J. Rucker, F. R. Jirik, and R. W. Doms. 1996. A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains. J. Virol. 70:6288-6295.
8. Bleul, C. C., M. Farzan, H. Choe, C. Parolin, I. Clark-Lewis, J. Sodroski, and T. A. Springer. 1996. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382:829-833.
9. Bleul, C. C., R. C. Fuhlbrigge, J. M. Casasnovas, A. Aiuti, and T. A. Springer. 1996. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J. Exp. Med. 184:1101-1109.
10. Bridger, G. J., R. T. Skerlj, S. Padmanabhan, S. A. Martellucci, G. W. Henson, S. Struyf, M. Witvrouw, D. Schols, and E. De Clercq. 1999. Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-azamacrocycles that inhibit HIV-1 and HIV-2 replication by antagonism of the chemokine receptor CXCR4. J. Med. Chem. 42:3971-3981.
11. Bridger, G. J., R. T. Skerlj, D. Thornton, S. Padmanabhan, S. A. Martellucci, G. W. Henson, M. J. Abrams, N. Yamamoto, K. De Vreese, R. Pauwels, and E. De Clercq. 1995. Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on the aromatic linker. J. Med. Chem. 38:366-378.
12. Chabot, D. J., and C. C. Broder. 2000. Substitutions in a homologous region of extracellular loop 2 of CXCR4 and CCR5 alter coreceptor activities for HIV-1 membrane fusion and virus entry. J. Biol. Chem. 275:23774-23782.
13. Choe, H., M. Farzan, Y. Sun, N. Sullivan, B. Rollins, P. D. Ponath, L. Wu, C. R. Mackay, G. LaRosa, W. Newman, N. Gerard, C. Gerard, and J. Sodroski. 1996. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85:1135-1148.
14. Cilliers, T., J. Nhlapo, M. Coetzer, D. Orlovic, T. Ketas, W. C. Olson, J. P. Moore, A. Trkola, and L. Morris. 2003. The CCR5 and CXCR4 coreceptors are both used by human immunodeficiency virus type 1 primary isolates from subtype C. J. Virol. 77:4449-4456.
15. + T cells. Science 270:1811-1815.
16. Cocchi, F., A. L. DeVico, A. Garzino-Demo, A. Cara, R. C. Gallo, and P. Lusso. 1996. The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Nat. Med. 2:1244-1247.
17. Connor, R. I, K. E. Sheridan, D. Ceradini, S. Choe, and N. R. Landau. 1997. Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J. Exp. Med. 185:621-628.
18. Crump, M. P., J. H. Gong, P. Loetscher, K. Rajarathnam, A. Amara, F. Arenzana-Seisdedos, J. L. Virelizier, M. Baggiolini, B. D. Sykes, and I. Clark-Lewis. 1997. Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1. EMBO J. 16:6996-7007.
19. Daelemans, D., D. Schols, M. Witvrouw, C. Pannecouque, S. Hatse, S. van Dooren, F. Hamy, T. Klimkait, E. De Clercq, and A. M. Van Damme. 2000. A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry. Mol. Pharmacol. 57:116-124.
20. Dean, M., M. Carrington, C. Winkler, G. A. Huttley, M. W. Smith, R. Allikmets, J. J. Goedert, S. P. Buchbinder, E. Vittinghoff, E. Gomperts, S. Donfield, D. Vlahov, R. Kaslow, A. Saah, C. Rinaldo, R. Detels, and S. J. O'Brien. 1996. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 273:1856-1862.
21. De Clercq, E., N. Yamamoto, R. Pauwels, M. Baba, D. Schols, H. Nakashima, J. Balzarini, Z. Debyser, B. A. Murrer, and D. Schwartz. 1992. Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event. Proc. Natl. Acad. Sci. USA 89:5286-5290.
22. De Clercq, E., N. Yamamoto, R. Pauwels, J. Balzarini, M. Witvrouw, K. De Vreese, Z. Debyser, B. Rosenwirth, P. Peichl, and R. Datema. 1994. Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100. Antimicrob. Agents Chemother. 38:668-674.
23. Deng, H., R. Liu, W. Ellmeier, S. Choe, D. Unutmaz, M. Burkhart, P. Di Marzio, S. Marmon, R. E. Sutton, C. M. Hill, C. B. Davis, S. C. Peiper, T. J. Schall, D. R. Littman, and N. R. Landau. 1996. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661-666.
24. De Vreese, K., V. Kofler-Mongold, C. Leutgeb, V. Weber, K. Vermeire, S. Schacht, J. Anne, E. De Clercq, R. Datema, and G. Werner. 1996. The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication. J. Virol. 70:689-696.
25. Donzella, G. A., D. Schols, S. W. Lin, J. A. Este, K. A. Nagashima, P. J. Maddon, G. P. Allaway, T. P. Sakmar, G. Henson, E. De Clercq, and J. P. Moore. 1998. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat. Med. 4:72-77.
26. Doranz, B. J., K. Grovit-Ferbas, M. P. Sharron, S. H. Mao, M. B. Goetz, E. S. Daar, R. W. Doms, and W. A. O'Brien. 1997. A small-molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor. J. Exp. Med. 186:1395-1400.
27. Doranz, B. J., J. Rucker, Y. Yi, R. J. Smyth, M. Samson, S. C. Peiper, M. Parmentier, R. G. Collman, and R. W. Doms. 1996. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 85:1149-1158.
28. Dragic, T., V. Litwin, G. P. Allaway, S. R. Martin, Y. Huang, K. A. Nagashima, C. Cayanan, P. J. Maddon, R. A. Koup, J. P. Moore, and W. A. Paxton. 1996. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667-673.
29. Este, J. A., C. Cabrera, E. De Clercq, S. Struyf, J. Van Damme, G. Bridger, R. T. Skerlj, M. J. Abrams, G. Henson, A. Gutierrez, B. Clotet, and D. Schols. 1999. Activity of different bicyclam derivatives against human immunodeficiency virus depends on their interaction with the CXCR4 chemokine receptor. Mol. Pharmacol. 55:67-73.
30. Feng, Y., C. C. Broder, P. E. Kennedy, and E. A. Berger. 1996. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272:872-877.
31. Garred, P., J. Eugen-Olsen, A. K. Iversen, T. L. Benfield, A. Svejgaard, and B. Hofmann. 1997. Dual effect of CCR5 Δ32 gene deletion in HIV-1-infected patients. Copenhagen AIDS Study Group. Lancet 349:1884.
32. Gerlach, L. O., R. T. Skerlj, G. J. Bridger, and T. W. Schwartz. 2001. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J. Biol. Chem. 276:14153-14160.
33. Glushakova, S., Y. Yi, J. C. Grivel, A. Singh, D. Schols, E. De Clercq, R. G. Collman, and L. Margolis. 1999. Preferential coreceptor utilization and cytopathicity by dual-tropic HIV-1 in human lymphoid tissue ex vivo. J. Clin. Investig. 104:R7-R11.
34. Gordon, C. J., M. A. Muesing, A. E. Proudfoot, C. A. Power, J. P. Moore, and A. Trkola. 1999. Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion. J. Virol. 73:684-694.
35. Hamy, F., E. R. Felder, G. Heizmann, J. Lazdins, F. Aboul-ela, G. Varani, J. Karn, and T. Klimkait. 1997. An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proc. Natl. Acad. Sci. USA 94:3548-3553.
36. Harada, S., Y. Koyanagi, and N. Yamamoto. 1985. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science 229:563-566.
37. 262 of the chemokine receptor CXCR4 impairs its coreceptor function for human immunodeficiency virus-1 entry and abrogates the antagonistic activity of AMD3100. Mol. Pharmacol. 60:164-173.
38. Hendrix, C. W., C. Flexner, R. T. MacFarland, C. Giandomenico, E. J. Fuchs, E. Redpath, G. Bridger, and G. W. Henson. 2000. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob. Agents Chemother. 44:1667-1673.
39. Kinter, A., A. Catanzaro, J. Monaco, M. Ruiz, J. Justement, S. Moir, J. Arthos, A. Oliva, L. Ehler, S. Mizell, R. Jackson, M. Ostrowski, J. Hoxie, R. Offord, and A. S. Fauci. 1998. CC-chemokines enhance the replication of T-tropic strains of HIV-1 in CD4(+) T cells: role of signal transduction. Proc. Natl. Acad. Sci. USA 95:11880-11885.
40. Labrosse, B., A. Brelot, N. Heveker, N. Sol, D. Schols, E. De Clercq, and M. Alizon. 1998. Determinants for sensitivity of human immunodeficiency virus coreceptor CXCR4 to the bicyclam AMD3100. J. Virol. 72:6381-6388.
41. Liu, Q. H., D. A. Williams, C. McManus, F. Baribaud, R. W. Doms, D. Schols, E. De Clercq, M. I. Kotlikoff, R. G. Collman, and B. D. Freedman. 2000. HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation. Proc. Natl. Acad. Sci. USA 97:4832-4837.
42. Liu, R., W. A. Paxton, S. Choe, D. Ceradini, S. R. Martin, R. Horuk, M. E. MacDonald, H. Stuhlmann, R. A. Koup, and N. R. Landau. 1996. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86:367-377.
43. Marechal, V., F. Arenzana-Seisdedos, J. M. Heard, and O. Schwartz. 1999. Opposite effects of SDF-1 on human immunodeficiency virus type 1 replication. J. Virol. 73:3608-3615.
44. McKnight, A., D. Wilkinson, G. Simmons, S. Talbot, L. Picard, M. Ahuja, M. Marsh, J. A. Hoxie, and P. R. Clapham. 1997. Inhibition of human immunodeficiency virus fusion by a monoclonal antibody to a coreceptor (CXCR4) is both cell type and virus strain dependent. J. Virol. 71:1692-1696.
45. Michael, N. L., J. A. Nelson, V. N. KewalRamani, G. Chang, S. J. O'Brien, J. R. Mascola, B. Volsky, M. Louder, G. C. White, D. R. Littman, R. Swanstrom, and T. R. O'Brien. 1998. Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 Δ32. J. Virol. 72:6040-6047.
46. Murakami, T., T. Nakajima, Y. Koyanagi, K. Tachibana, N. Fujii, H. Tamamura, N. Yoshida, M. Waki, A. Matsumoto, O. Yoshie, T. Kishimoto, N. Yamamoto, and T. Nagasawa. 1997. A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. J. Exp. Med. 186:1389-1393.
47. Oberlin, E., A. Amara, F. Bachelerie, C. Bessia, J. L. Virelizier, F. Arenzana-Seisdedos, O. Schwartz, J. M. Heard, I. Clark-Lewis, D. F. Legler, M. Loetscher, M. Baggiolini, and B. Moser. 1996. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382:833-835.
48. Perno, C. F., and R. Yarchoan. 1993. Culture of HIV in monocytes and macrophages, p. 12.4.1-12.4.11. In J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, and W. Strober (ed.), Current protocols in immunology. J. Wiley & Sons, New York, N.Y.
49. 2+ signaling by fluorometric imaging plate reader (FLIPR) and flow cytometry. Cytometry 51A:35-45.
50. Ratner, L., W. Haseltine, R. Patarca, K. J. Livak, B. Starcich, S. F. Josephs, E. R. Doran, J. A. Rafalski, E. A. Whitehorn, and K. Baumeister. 1985. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313:277-284.
51. Reynes, J., R. Rouzier, T. Kanouni, V. Baillat, B. Baroudy, A. Keung, C. Hogan, M. Markowitz, and M. Laughlin. 2002. SCH C: safety and antiviral effects of a CCR5 receptor antagonist in HIV-1 infected subjects, p. 53. Program Abstr. 9th Conf. Retrovir. Opportunistic Infect., Seattle, Wash.
52. Samson, M., F. Libert, B. J. Doranz, J. Rucker, C. Liesnard, C. M. Farber, S. Saragosti, C. Lapoumeroulie, J. Cognaux, C. Forceille, G. Muyldermans, C. Verhofstede, G. Burtonboy, M. Georges, T. Imai, S. Rana, Y. Yi, R. J. Smyth, R. G. Collman, R. W. Doms, G. Vassart, and M. Parmentier. 1996. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722-725.
53. Schmidtmayerova, H., B. Sherry, and M. Bukrinsky. 1996. Chemokines and HIV replication. Nature 382:767.
54. Schols, D., S. Claes, E. De Clercq, C. Hendrix, G. Bridger, G. Calandra, G. Henson, S. Fransen, W. Huang, J. Whitcomb, and C. Petropoulos. 2002. AMD-3100, a CXCR4 antagonist, reduced HW viral load and X4 virus levels in humans, p. 53. Program Abstr. 9th Conf. Retrovir. Opportunistic Infect., Seattle, Wash.
55. Schols, D, J. A. Este, C. Cabrera, and E. De Clercq. 1998. T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1α contains mutations in the envelope gp120 but does not show a switch in coreceptor use. J. Virol. 72:4032-4037.
56. Schols, D., S. Struyf, J. Van Damme, J. A. Este, G. Henson, and E. De Clercq. 1997. Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J. Exp. Med. 186:1383-1388.
57. Schuitemaker, H., M. Root, N. A. Kootstra, M. W. Dercksen, R. E. de Goede, R. P. van Steenwijk, J. M. Lange, J. K. Schattenkerk, F. Miedema, and M. Tersmette. 1992. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J. Virol. 66:1354-1360.
58. Signoret, N., J. Oldridge, A. Pelchen-Matthews, P. J. Klasse, T. Tran, L. F. Brass, M. M. Rosenkilde, T. W. Schwartz, W. Holmes, W. Dallas, M. A. Luther, T. N. Wells, J. A. Hoxie, and M. Marsh. 1997. Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4. J. Cell Biol. 139:651-664.
59. Signoret, N., M. M. Rosenkilde, P. J. Klasse, T. W. Schwartz, M. H. Malim, J. A. Hoxie, and M. Marsh. 1998. Differential regulation of CXCR4 and CCR5 endocytosis. J. Cell Sci. 111:2819-2830.
60. Simmons, G., P. R. Clapham, L. Picard, R. E. Offord, M. M. Rosenkilde, T. W. Schwartz, R. Buser, T. N. Wells, and A. E. Proudfoot. 1997. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science 276:276-279.
61. Strizki, J. M., S. Xu, N. E. Wagner, L. Wojcik, J. Liu, Y. Hou, M. Endres, A. Palani, S. Shapiro, J. W. Clader, W. J. Greenlee, J. R. Tagat, S. McCombie, K. Cox, A. B. Fawzi, C. C. Chou, C. Pugliese-Sivo, L. Davies, M. E. Moreno, D. D. Ho, A. Trkola, C. A. Stoddart, J. P. Moore, G. R. Reyes, and B. M. Baroudy. 2001. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc. Natl. Acad. Sci. USA 98:12718-12723.
62. Trkola, A., C. Gordon, J. Matthews, E. Maxwell, T. Ketas, L. Czaplewski, A. E. Proudfoot, and J. P. Moore. 1999. The CC-chemokine RANTES increases the attachment of human immunodeficiency virus type 1 to target cells via glycosaminoglycans and also activates a signal transduction pathway that enhances viral infectivity. J. Virol. 73:6370-6379.
63. Tsamis, F., S. Gavrilov, F. Kajumo, C. Seibert, S. Kuhmann, T. Ketas, A. Trkola, A. Palani, J. W. Clader, J. R. Tagat, S. McCombie, B. Baroudy, J. P. Moore, T. P. Sakmar, and T. Dragic. 2003. Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry. J. Virol. 77:5201-5208.
64. Van Damme, J., P. Proost, J. P. Lenaerts, and G. Opdenakker. 1992. Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. J. Exp. Med. 176:59-65.
65. Zhang, Y. J., and J. P. Moore. 1999. Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry? J. Virol. 73:3443-3448.