Inhibition of CCR5-mediated infection by diverse R5 and R5X4 HIV and SIV isolates using novel small molecule inhibitors of CCR5: Effects of viral diversity, target cell and receptor density

Antiviral Research

Volumn 68, Issue 2, 2005, Pages 96-108

  Willey, Samantha ^a,b   Peters, Paul J ^a   Sullivan, W Matthew ^a   Dorr, Patrick ^c   Perros, Manos ^c   Clapham, Paul R ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b Windeyer Institute   (United Kingdom)

^c PFIZER INC   (United States)

Author keywords

CCR5; Coreceptor inhibitor; HAART; HIV coreceptors

Indexed keywords

CHEMOKINE RECEPTOR; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CCR3; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; CHEMOKINE RECEPTOR CCR8; CHEMOKINE RECEPTOR CXCR4; CHEMOKINE RECEPTOR CXCR6; UK 383990; UK 387323; UK 396794; UK 400343; UK 403341; UNCLASSIFIED DRUG; VIRUS RECEPTOR;

ARTICLE; CELL SURFACE; CELL TYPE; CONTROLLED STUDY; CROSS REACTION; DRUG MECHANISM; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; MACROPHAGE; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN DETERMINATION; SIMIAN IMMUNODEFICIENCY VIRUS; TARGET CELL; VIRUS REPLICATION; VIRUS STRAIN;

AMIDES; ANTIGENS, CD4; CELL LINE; DOWN-REGULATION; HIV INFECTIONS; HIV-1; HIV-2; HUMANS; MACROPHAGES; MONOCYTES; QUATERNARY AMMONIUM COMPOUNDS; RANTES; RECEPTORS, CCR5; RECEPTORS, CELL SURFACE; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; SIMIAE; SIMIAN IMMUNODEFICIENCY VIRUS;

EID: 27644593773     PISSN: 01663542     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.antiviral.2005.07.006     Document Type: Article

References (78)

1. S. Abel, E. Van der Ryst, M. Muirhead, M. Rosario, A. Edgington, and G. Weissberger Pharmacokinetics of single and multiple oral doses of UK-427,857 - a novel CCR5 antagonist in healthy volunteers 10th Conference on Retroviruses and Opportunistic Infections Boston, MA, USA, 10-14 February 2003 (abstracts, no. 547)
2. G. Alkhatib, C. Combadiere, C.C. Broder, Y. Feng, P.E. Kennedy, P.M. Murphy, and E.A. Berger CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1 Science 272 1996 1955 1958
3. M. Baba, O. Nishimura, N. Kanzaki, M. Okamoto, H. Sawada, Y. Iizawa, M. Shiraishi, Y. Aramaki, K. Okonogi, Y. Ogawa, K. Meguro, and M. Fujino A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity Proc. Natl. Acad. Sci. U.S.A. 96 1999 5698 5703
4. C.G. Barber CCR5 antagonists for the treatment of HIV Curr. Opin. Investig. Drugs 5 2004 851 861
5. E.A. Berger, P.M. Murphy, and J.M. Farber Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease Annu. Rev. Immunol. 17 1999 657 700
6. A. Bjorndal, H. Deng, M. Jansson, J.R. Fiore, C. Colognesi, A. Karlsson, J. Albert, G. Scarlatti, D.R. Littman, and E.M. Fenyo Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype J. Virol. 71 1997 7478 7487
7. A. Bobkov, R. Cheingsong-Popov, M. Garaev, A. Rzhaninova, P. Kaleebu, S. Beddows, M.H. Bachmann, J.I. Mullins, J. Louwagie, W. Janssens, G. van der Groen, F. McCutchan, and J. Weber Identification of an env G subtype and heterogeneity of HIV-1 strains in the Russian Federation and Belarus AIDS 8 1994 1649 1655
8. M.T. Boyd, G.R. Simpson, A.J. Cann, M.A. Johnson, and R.A. Weiss A single amino acid substitution in the V1 loop of human immunodeficiency virus type 1 gp120 alters cellular tropism J. Virol. 67 1993 3649 3652
9. B.G. Brenner, D. Turner, and M.A. Wainberg HIV-1 drug resistance: can we overcome? Expert. Opin. Biol. Ther. 2 2002 751 761
10. D. Cecilia, V.N. KewalRamani, J. O'Leary, B. Volsky, P. Nyambi, S. Burda, S. Xu, D.R. Littman, and S. Zolla-Pazner Neutralization profiles of primary human immunodeficiency virus type 1 isolates in the context of coreceptor usage J. Virol. 72 1998 6988 6996
11. C. Cheng-Mayer, C. Weiss, D. Seto, and J.A. Levy Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus Proc. Natl. Acad. Sci. U.S.A. 86 1989 8575 8579
12. P.R. Clapham, and A. McKnight Cell surface receptors, virus entry and tropism of primate lentiviruses J. Gen. Virol. 83 2002 1809 1829
13. P.R. Clapham, A. McKnight, and R.A. Weiss Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4 J. Virol. 66 1992 3531 3537
14. P.R. Clapham, J.D. Reeves, G. Simmons, N. Dejucq, S. Hibbitts, and A. McKnight HIV coreceptors, cell tropism and inhibition by chemokine receptor ligands Mol. Membr. Biol. 16 1999 49 55
15. F. Cocchi, A.L. DeVico, A. Garzino-Demo, S.K. Arya, R.C. Gallo, and P. Lusso Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells Science 270 1995 1811 1815
16. C.J. Cohen, A. Dusek, J. Green, E.L. Johns, E. Nelson, and M.A. Recny Long-term treatment with subcutaneous T-20, a fusion inhibitor, in HIV-infected patients: patient satisfaction and impact on activities of daily living AIDS Patient Care STDS 16 2002 327 335
17. R. Collman, J.W. Balliet, S.A. Gregory, H. Friedman, D.L. Kolson, N. Nathanson, and A. Srinivasan An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1 J. Virol. 66 1992 7517 7521
18. A.G. Dalgleish, P.C. Beverley, P.R. Clapham, D.H. Crawford, M.F. Greaves, and R.A. Weiss The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus Nature 312 1984 763 767
19. M.D. Daniel, N.L. Letvin, N.W. King, M. Kannagi, P.K. Sehgal, R.D. Hunt, P.J. Kanki, M. Essex, and R.C. Desrosiers Isolation of T-cell tropic HTLV-III-like retrovirus from macaques Science 228 1985 1201 1204
20. M.D. Daniel, Y. Li, Y.M. Naidu, P.J. Durda, D.K. Schmidt, C.D. Troup, D.P. Silva, J.J. MacKey, H.W. Kestler 3rd, P.K. Sehgal, N.W. King, Y. Ohta, M. Hayami, and R.C. Desrosiers Simian immunodeficiency virus from African green monkeys J. Virol. 62 1988 4123 4128
21. E. De Clercq New developments in anti-HIV chemotherapy Biochim. Biophys. Acta 1587 2002 258 275
22. E. De Clercq, N. Yamamoto, R. Pauwels, J. Balzarini, M. Witvrouw, K. De Vreese, Z. Debyser, B. Rosenwirth, P. Peichl, R. Datema, D. Thornton, R. Skerlj, F. Gaul, S. Padmanabhan, D. Bridger, G. Henson, and M. Abrams Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100 Antimicrob. Agents Chemother. 38 1994 668 674
23. A.M. de Roda Husman, R.P. van Rij, H. Blaak, S. Broersen, and H. Schuitemaker Adaptation to promiscuous usage of chemokine receptors is not a prerequisite for human immunodeficiency virus type 1 disease progression J. Infect Dis. 180 1999 1106 1115
24. Dean, M., Carrington, M., Winkler, C., Huttley, G.A., Smith, M.W., Allikmets, R., Goedert, J.J., Buchbinder, S.P., Vittinghoff, E., Gomperts, E., Donfield, S., Vlahov, D., Kaslow, R., Saah, A., Rinaldo, C., Detels, R., O'Brien, S.J., 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.
25. N. Dejucq, G. Simmons, and P.R. Clapham Expanded tropism of primary human immunodeficiency virus type 1 R5 strains to CD4(+) T-cell lines determined by the capacity to exploit low concentrations of CCR5 J. Virol. 73 1999 7842 7847
26. H. Deng, 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 Identification of a major co-receptor for primary isolates of HIV-1 Nature 381 1996 661 666
27. H.K. Deng, D. Unutmaz, V.N. KewalRamani, and D.R. Littman Expression cloning of new receptors used by simian and human immunodeficiency viruses Nature 388 1997 296 300
28. D.S. Dimitrov, X. Xiao, D.J. Chabot, and C.C. Broder HIV coreceptors J. Membr. Biol. 166 1998 75 90
29. G.A. Donzella, 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 AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor Nat. Med. 4 1998 72 77
30. B.J. Doranz, Z.H. Lu, J. Rucker, T.Y. Zhang, M. Sharron, Y.H. Cen, Z.X. Wang, H.H. Guo, J.G. Du, M.A. Accavitti, R.W. Doms, and S.C. Peiper Two distinct CCR5 domains can mediate coreceptor usage by human immunodeficiency virus type 1 J. Virol. 71 1997 6305 6314
31. P. Dorr, G. Macartney, G. Rickett, C. Smith-Burchnell, S. Dobbs, J. Mori, P. Griffin, J. Lok, R. Irvine, M. Westby, C. Hitchcock, B. Stammen, D. Price, D. Armour, A. Wood, and M. Perros UK-427,857, a novel small molecule HIV entry inhibitor is a specific antagonist of the chemokine receptor CCR5 10th Conference on Retroviruses and Opportunistic Infections Boston, MA, USA, 10-14 February 2003 (abstracts, no. 12)
32. T. Dragic, 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 HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5 Nature 381 1996 667 673
33. T. Dragic, A. Trkola, D.A. Thompson, E.G. Cormier, F.A. Kajumo, E. Maxwell, S.W. Lin, W. Ying, S.O. Smith, T.P. Sakmar, and J.P. Moore A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5 Proc. Natl. Acad. Sci. U.S.A. 97 2000 5639 5644
34. A.L. Edinger, A. Amedee, K. Miller, B.J. Doranz, M. Endres, M. Sharron, M. Samson, Z.H. Lu, J.E. Clements, M. Murphey-Corb, S.C. Peiper, M. Parmentier, C.C. Broder, and R.W. Doms Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains Proc. Natl. Acad. Sci. U.S.A. 94 1997 4005 4010
35. R.M. Gulick, J.W. Mellors, D. Havlir, J.J. Eron, C. Gonzalez, D. McMahon, D.D. Richman, F.T. Valentine, L. Jonas, A. Meibohm, E.A. Emini, and J.A. Chodakewitz Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy N. Engl. J. Med. 337 1997 734 739
36. S.M. Hammer, K.E. Squires, M.D. Hughes, J.M. Grimes, L.M. Demeter, J.S. Currier, J.J. Eron Jr., J.E. Feinberg, H.H. Balfour Jr., L.R. Deyton, J.A. Chodakewitz, M.A. Fischl AIDS Clinical Trials Group 320 Study Team A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less N. Engl. J. Med. 337 1997 725 733
37. C.W. Hendrix, C. Flexner, R.T. MacFarland, C. Giandomenico, E.J. Fuchs, E. Redpath, G. Bridger, and G.W. Henson Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers Antimicrob. Agents Chemother. 44 2000 1667 1673
38. Y. Huang, W.A. Paxton, S.M. Wolinsky, A.U. Neumann, L. Zhang, T. He, S. Kang, D. Ceradini, Z. Jin, K. Yazdanbakhsh, K. Kunstman, D. Erickson, E. Dragon, N.R. Landau, J. Phair, D.D. Ho, and R.A. Koup The role of a mutant CCR5 allele in HIV-1 transmission and disease progression Nat. Med. 2 1996 1240 1243
39. D.C. Kalter, M. Nakamura, J.A. Turpin, L.M. Baca, D.L. Hoover, C. Dieffenbach, P. Ralph, H.E. Gendelman, and M.S. Meltzer Enhanced HIV replication in macrophage colony-stimulating factor-treated monocytes J. Immunol. 146 1991 298 306
40. G.R. Kaufmann, M. Bloch, J.J. Zaunders, D. Smith, and D.A. Cooper Long-term immunological response in HIV-1-infected subjects receiving potent antiretroviral therapy AIDS 14 2000 959 969
41. T.J. Ketas, P.J. Klasse, C. Spenlehauer, M. Nesin, I. Frank, M. Pope, J.M. Strizki, G.R. Reyes, B.M. Baroudy, and J.P. Moore Entry inhibitors SCH-C, RANTES, and T-20 block HIV type 1 replication in multiple cell types AIDS Res. Hum. Retroviruses 19 2003 177 186
42. R. Kikukawa, Y. Koyanagi, S. Harada, N. Kobayashi, M. Hatanaka, and N. Yamamoto Differential susceptibility to the acquired immunodeficiency syndrome retrovirus in cloned cells of human leukemic T-cell line Molt-4 J. Virol. 57 1986 1159 1162
43. D. Klatzmann, E. Champagne, S. Chamaret, J. Gruest, D. Guetard, T. Hercend, J.C. Gluckman, and L. Montagnier T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV Nature 312 1984 767 768
44. T.N. Kledal, M.M. Rosenkilde, F. Coulin, G. Simmons, A.H. Johnsen, S. Alouani, C.A. Power, H.R. Luttichau, J. Gerstoft, P.R. Clapham, I. Clark-Lewis, T.N.C. Wells, and T.W. Schwartz A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus Science 277 1997 1656 1659
45. S.E. Kuhmann, P. Pugach, K.J. Kunstman, J. Taylor, R.L. Stanfield, A. Snyder, J.M. Strizki, J. Riley, B.M. Baroudy, I.A. Wilson, B.T. Korber, S.M. Wolinsky, and J.P. Moore Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor J. Virol. 78 2004 2790 2807
46. R. Liu, W.A. Paxton, S. Choe, D. Ceradini, S.R. Martin, R. Horuk, M.E. MacDonald, H. Stuhlmann, R.A. Koup, and N.R. Landau Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply exposed individuals to HIV-1 infection Cell 86 1996 367 377
47. M. Mack, B. Luckow, P.J. Nelson, J. Cihak, G. Simmons, P.R. Clapham, N. Signoret, M. Marsh, M. Stangassinger, F. Borlat, T.N. Wells, D. Schlondorff, and A.E. Proudfoot Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity J. Exp. Med. 187 1998 1215 1224
48. K. Maeda, H. Nakata, H. Ogata, Y. Koh, T. Miyakawa, and H. Mitsuya The current status of, and challenges in, the development of CCR5 inhibitors as therapeutics for HIV-1 infection Curr. Opin. Pharmacol. 4 2004 447 452
49. A. McKnight, P.R. Clapham, and R.A. Weiss HIV-2 and SIV infection of nonprimate cell lines expressing human CD4: restrictions to replication at distinct stages Virology 201 1994 8 18
50. A. McKnight, M.T. Dittmar, J. Moniz-Periera, K. Ariyoshi, J.D. Reeves, S. Hibbitts, D. Whitby, E. Aarons, A.E. Proudfoot, H. Whittle, and P.R. Clapham A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4 J. Virol. 72 1998 4065 4071
51. H. Moriuchi, M. Moriuchi, C. Combadiere, P.M. Murphy, and A.S. Fauci CD8+ T-cell-derived soluble factor(s), but not beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta, suppress HIV-1 replication in monocyte/macrophages Proc. Natl. Acad. Sci. U.S.A. 93 1996 15341 15345
52. D.E. Mosier, G.R. Picchio, R.J. Gulizia, R. Sabbe, P. Poignard, L. Picard, R.E. Offord, D.A. Thompson, and J. Wilken Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus type 1 infection in vivo or rapidly select for CXCR4-using variants J. Virol. 73 1999 3544 3550
53. M. Murphey-Corb, L.N. Martin, S.R. Rangan, G.B. Baskin, B.J. Gormus, R.H. Wolf, W.A. Andes, M. West, and R.C. Montelaro Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys Nature 321 1986 435 437
54. C. Napier, P. Dorr, R. Gladue, R. Halliday, D. Leishman, I. Machin, R. Mitchel, A. Nedderman, M. Perros, D. Roffey, D. Walker, and R. Webster The preclinical pharmacokinetics and safety pharmacology of the anti-HIV CCR5 antagonist, UK-427,857 10th Conference on Retroviruses and Opportunistic Infections Boston, MA, USA, 10-14 February 2003 (abstracts, no. 546a)
55. T. Oravecz, M. Pall, and M.A. Norcross Beta-chemokine inhibition of monocytotropic HIV-1 infection. Interference with a postbinding fusion step J. Immunol. 157 1996 1329 1332
56. F.J. Palella Jr., K.M. Delaney, A.C. Moorman, M.O. Loveless, J. Fuhrer, G.A. Satten, D.J. Aschman, and S.D. Holmberg Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection N. Engl. J. Med. 338 1998 853 860
57. P.J. Peters, J. Bhattacharya, S. Hibbitts, M.T. Dittmar, G. Simmons, J. Bell, P. Simmonds, and P.R. Clapham Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages J. Virol. 78 2004 6915 6926
58. E.J. Platt, K. Wehrly, S.E. Kuhmann, B. Chesebro, and D. Kabat Effects of CCR5 and CD4 cell surface concentrations on infections by macrophage tropic isolates of human immunodeficiency virus type 1 J. Virol. 72 1998 2855 2864
59. E.J. Platt, J.P. Durnin, and D. Kabat Kinetic factors control efficiencies of cell entry, efficacies of entry inhibitors, and mechanisms of adaptation of human immunodeficiency virus J. Virol. 79 2005 4347 4356
60. A.L. Pozniac, G. Fätkenheuer, M.A. Johnson, I.M. Hoepelman, J.K. Rockstroh, F. Goebel, S. Abel, I. James, M. Rosario, C. Medhurst, J.L. Sullivan, M. Youle, and E. Van Der Ryst Effect of short-term monotherapy with UK-427,857 on viral load in HIV-infected patients 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy Chicago, IL, 14-17 September 2003 (abstracts, no. H-443)
61. J.D. Reeves, S.A. Gallo, N. Ahmad, J.L. Miamidian, P.E. Harvey, M. Sharron, S. Pohlmann, J.N. Sfakianos, C.A. Derdeyn, R. Blumenthal, E. Hunter, and R.W. Doms Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics Proc. Natl. Acad. Sci. U.S.A. 99 2002 16249 16254
62. J.D. Reeves, J.L. Miamidian, M.J. Biscone, F.H. Lee, N. Ahmad, T.C. Pierson, and R.W. Doms Impact of mutations in the coreceptor binding site on human immunodeficiency virus type 1 fusion, infection, and entry inhibitor sensitivity J. Virol. 78 2004 5476 5485
63. M. Samson, 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 Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene Nature 382 1996 722 725
64. U. Sauermann, J. Schneider, J. Mous, U. Brunckhorst, I. Schedel, K.D. Jentsch, and G. Hunsmann Molecular cloning and characterization of a German HIV-1 isolate AIDS Res. Hum. Retroviruses 6 1990 813 823
65. M. Seto, N. Miyamoto, K. Aikawa, Y. Aramaki, N. Kanzaki, Y. Iizawa, M. Baba, and M. Shiraishi Orally active CCR5 antagonists as anti-HIV-1 agents. Part 3. Synthesis and biological activities of 1-benzazepine derivatives containing a sulfoxide moiety Bioorg. Med. Chem. 13 2005 363 386
66. G. Simmons, P.R. Clapham, L. Picard, R.E. Offord, M.M. Rosenkilde, T.W. Schwartz, R. Buser, T.N.C. Wells, and A.E. Proudfoot Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist Science 276 1997 276 279
67. G. Simmons, D. Wilkinson, J.D. Reeves, M.T. Dittmar, S. Beddows, J. Weber, G. Carnegie, U. Desselberger, P.W. Gray, R.A. Weiss, and P.R. Clapham Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry J. Virol. 70 1996 8355 8360
68. Y. Soda, N. Shimizu, A. Jinno, H.Y. Liu, K. Kanbe, T. Kitamura, and H. Hoshino Establishment of a new system for determination of coreceptor usages of HIV based on the human glioma NP-2 cell line Biochem. Biophys. Res. Commun. 258 1999 313 321
69. J.M. Strizki, 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 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. U.S.A. 98 2001 12718 12723
70. J.R. Tagat, S.W. McCombie, D. Nazareno, M.A. Labroli, Y. Xiao, R.W. Steensma, J.M. Strizki, B.M. Baroudy, K. Cox, J. Lachowicz, G. Varty, and R. Watkins Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]-4-[4-[2-methoxy-1(R) -4-(trifluoromethyl)phenyl]-ethyl-3(S)-methyl-1-piperazinyl]-4-methylpiperidine (Sch-417690/Sch-D), a potent, highly selective, and orally bioavailable CCR5 antagonist J. Med. Chem. 47 2004 2405 2408
71. M. Tersmette, R.E. de Goede, B.J. Al, I.N. Winkel, R.A. Gruters, H.T. Cuypers, H.G. Huisman, and F. Miedema Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex J. Virol. 62 1988 2026 2032
72. A. Trkola, S.E. Kuhmann, J.M. Strizki, E. Maxwell, T. Ketas, T. Morgan, P. Pugach, S. Xu, L. Wojcik, J. Tagat, A. Palani, S. Shapiro, J.W. Clader, S. McCombie, G.R. Reyes, B.M. Baroudy, and J.P. Moore HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use Proc. Natl. Acad. Sci. U.S.A. 99 2002 395 400
73. R.P. van Rij, J.A. Visser, R.M. van Praag, R. Rientsma, J.M. Prins, J.M. Lange, and H. Schuitemaker Both R5 and X4 human immunodeficiency virus type 1 variants persist during prolonged therapy with five antiretroviral drugs J. Virol. 76 2002 3054 3058
74. M. Westby, C. Smith-Burchnell, J. Mori, M.G. Lewis, R. Mansfield, J. Whitcomb, C. Petropoulos, and M. Perros In vitro escape of R5 primary isolates from the CCR5 antagonist, UK-427,857, is difficult and involves continued use of the CCR5 receptor XIII International HIV Drug Resistance Workshop Tenerife, Canary Islands, Spain, 8-12 June 2004 (Antiviral Therapy, abstracts, no. 6)
75. M. Westby, C. Smith-Burchnell, D. Hamilton, J. Mori, M. Macartney, N. Robas, B. Irvine, M. Fidock, F. Perruccio, J. Mills, C. Burt, C.G. Barber, P. Stephenson, P. Dorr, and M. Perros Structurally related HIV co-receptor antagonists bind to similar regions of CCR5 but have differential activities against maraviroc (UK427,857)-resistant primary isolates 12th Conference on Retroviruses and Opportunistic Infections Boston, MA, USA, 22-25 February 2005 (abstracts, no. 96)
76. B.J. Willett, L. Picard, M.J. Hosie, J.D. Turner, K. Adema, and P.R. Clapham Shared usage of the chemokine receptor CXCR4 by the feline and human immunodeficiency viruses J. Virol. 71 1997 6407 6415
77. S.J. Willey, J.D. Reeves, R. Hudson, K. Miyake, N. Dejucq, D. Schols, E. De Clercq, J. Bell, A. McKnight, and P.R. Clapham 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 2003 6138 6152
78. P.G. Yeni, S.M. Hammer, C.C. Carpenter, D.A. Cooper, M.A. Fischl, J.M. Gatell, B.G. Gazzard, M.S. Hirsch, D.M. Jacobsen, D.A. Katzenstein, J.S. Montaner, D.D. Richman, M.S. Saag, M. Schechter, R.T. Schooley, M.A. Thompson, S. Vella, and P.A. Volberding Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society, USA Panel JAMA 288 2002 222 235