Characterization of a human immunodeficiency virus type 1 V3 deletion mutation that confers resistance to CCR5 inhibitors and the ability to use aplaviroc-bound receptor

Journal of Virology

Volumn 83, Issue 8, 2009, Pages 3798-3809

  Nolan, Katrina M ^a   Del Prete, Gregory Q ^a   Jordan, Andrea P O ^a   Haggarty, Beth ^a   Romano, Josephine ^a   Leslie, George J ^a   Hoxie, James A ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APLAVIROC; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 2D7; MONOCLONAL ANTIBODY 2G12; MONOCLONAL ANTIBODY 3A9; MONOCLONAL ANTIBODY 45531; MONOCLONAL ANTIBODY 4E10; MONOCLONAL ANTIBODY B12; UNCLASSIFIED DRUG; 873140 COMPOUND; BENZOIC ACID DERIVATIVE; GLYCOPROTEIN GP 120; GP120 PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; PIPERAZINE DERIVATIVE; SPIRO COMPOUND;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANTIVIRAL RESISTANCE; ARTICLE; CHIMERA; CLADISTICS; CONCENTRATION RESPONSE; DELETION MUTANT; DRUG RECEPTOR BINDING; EMBRYO; EXTRACELLULAR SPACE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IC 50; NONHUMAN; NUCLEOTIDE SEQUENCE; POINT MUTATION; PRIORITY JOURNAL; VIROGENESIS; VIRUS CHARACTERIZATION; VIRUS INFECTIVITY; VIRUS MUTANT; VIRUS NEUTRALIZATION; CELL LINE; DNA SEQUENCE; DRUG EFFECT; GENE DELETION; GENETICS; IMMUNOLOGY; METABOLISM; MOLECULAR GENETICS; PHYSIOLOGY; PROTEIN BINDING; SERODIAGNOSIS; VIRUS ENTRY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTIBODIES, MONOCLONAL; BENZOATES; CELL LINE; DRUG RESISTANCE, VIRAL; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP120; HIV FUSION INHIBITORS; HIV-1; HUMANS; MOLECULAR SEQUENCE DATA; NEUTRALIZATION TESTS; PIPERAZINES; PROTEIN BINDING; RECEPTORS, CCR5; SEQUENCE ANALYSIS, DNA; SEQUENCE DELETION; SPIRO COMPOUNDS; VIRUS INTERNALIZATION;

EID: 64049109934     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.01751-08     Document Type: Article

References (91)

1. Alexander, W. A., B. Moss, and T. R. Fuerst. 1992. Regulated expression of foreign genes in vaccinia virus under the control of bacteriophage T7 RNA polymerase and the Escherichia coli lac repressor. J. Virol. 66:2934-2942.
2. 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-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272: 1955-1958.
3. Baba, M., H. Mikake, X. Wang, M. Okamoto, and K. Takashima. 2007. Isolation and characterization of human immunodeficiency virus type 1 resistant to the small-molecule CCR5 antagonist TAK-652. Antimicrob. Agents Chemother. 51:707-715. (Pubitemid 46185293)
4. Billick, E., C. Seibert, P. Pugagh, T. Ketas, A. Trkola, M. J. Endres, N. J. Murgolo, E. Coates, G. R. Reyes, B. M. Baroudy, T. P. Sakmar, J. P. Moore, and S. E. Kuhmann. 2004. The differential sensitivity of human and rhesus macaque CCR5 to small-molecule inhibitors of human immunodeficiency virus type 1 entry is explained by a single amino acid difference and suggests a mechanism of action for these inhibitors. J. Virol. 78:4134-4144. (Pubitemid 38437219)
5. Braibant, M., S. Brunet, D. Costagliola, C. Rouzioux, H. Agut, H. Katinger, B. Autran, and F. Barin. 2006. Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity. AIDS 20:1923-1930.
6. Cao, J., N. Sullivan, E. Desjardin, C. Parolin, J. Robinson, R. Wyatt, and J. Sodroski. 1997. Replication and neutralization of human immunodeficiency virus type 1 lacking the V1 and V2 variable loops of the gp120 envelope glycoprotein. J. Virol. 71:9808-9812. (Pubitemid 27492434)
7. Chan, D. C., D. Fass, J. M. Berger, and P. S. Kim. 1997. Core structure of gp41 from the HIV envelope glycoprotein. Cell 89:263-273.
8. Chen, B., E. M. Vogan, H. Gong, J. J. Skehel, D. C. Wiley, and S. C. Harrison. 2005. Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433:834-841.
9. Chen, B. K., K. Saksela, R. Andino, and D. Baltimore. 1994. Distinct modes of human immunodeficiency virus type 1 proviral latency revealed by superinfection of nonproductively infected cell lines with recombinant luciferase-encoding viruses. J. Virol. 68:654-660. (Pubitemid 24022165)
10. 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.
11. 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. (Pubitemid 27098147)
12. Cormier, E. G., and T. Dragic. 2002. The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor. J. Virol. 76:8953-8957.
13. Cormier, E. G., M. Persuh, D. A. Thompson, S. W. Lin, T. P. Sakmar, W. C. Olson, and T. Dragic. 2000. Specific interaction of CCR5 amino-terminal domain peptides containing sulfotyrosines with HIV-1 envelope glycoprotein gp120. Proc. Natl. Acad. Sci. USA 97:5762-5767.
14. Cormier, E. G., D. N. Tran, L. Yukhayeva, W. C. Olson, and T. Dragic. 2001. Mapping the determinants of the CCR5 amino-terminal sulfopeptide interaction with soluble human immunodeficiency virus type 1 gp120-CD4 complexes. J. Virol. 75:5541-5549. (Pubitemid 32488147)
15. 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. (Pubitemid 26322495)
16. Demarest, J. F., S. S. Sparks, K. Schell, S. Shibayama, C. B. McDanal, L. Fang, K. K. Adkison, A. Shachoy-Clark, and S. C. Piscitelli. 2008. In vitro and clinical investigation of the relationship between CCR5 receptor occupancy and anti-HIV activity of aplaviroc. J. Clin. Pharmacol. 48:1179-1188.
17. 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.
18. Doms, R. W., and J. P. Moore. 2000. HIV-1 membrane fusion: targets of opportunity. J. Cell Biol. 151:F9-14.
19. Doranz, B. J., 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. 1997. Two distinct CCR5 domains can mediate coreceptor usage by human immunodeficiency virus type 1. J. Virol. 71:6305-6314. (Pubitemid 27355283)
20. 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 β-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 85:1149-1158.
21. Dorr, P., M. Westby, S. Dobbs, P. Griffin, B. Irvine, M. Macartney, J. Mori, G. Rickett, C. Smith-Burchnell, C. Napier, R. Webster, D. Armour, D. Price, B. Stammen, A. Wood, and M. Perros. 2005. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob. Agents Chemother. 49:4721-4732. (Pubitemid 41552605)
22. + cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667-673.
23. Dragic, T., A. Trkola, S. W. Lin, K. A. Nagashima, F. Kajumo, L. Zhao, W. C. Olson, L. Wu, C. R. Mackay, G. P. Allaway, T. P. Sakmar, J. P. Moore, and P. J. Maddon. 1998. Amino-terminal substitutions in the CCR5 coreceptor impair gp120 binding and human immunodeficiency virus type 1 entry. J. Virol. 72:279-285. (Pubitemid 28048838)
24. Dragic, T., 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. 2000. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc. Natl. Acad. Sci. USA 97:5639-5644.
25. Edinger, A. L., and R. W. Doms. 1999. A cell-cell fusion assay to monitor HIV-1 Env interactions with chemokine receptors. Methods Mol. Med. 17:41-49. doi:10.1385/0-89603-369-4:41.
26. Endres, M. J., P. R. Clapham, M. Marsh, M. Ahuja, J. D. Turner, A. McKnight, J. F. Thomas, B. Stoebenau-Haggarty, S. Choe, P. J. Vance, T. N. Wells, C. A. Power, S. S. Sutterwala, R. W. Doms, N. R. Landau, and J. A. Hoxie. 1996. CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell 87:745-756.
27. Farzan, M., T. Mirzabekov, P. Kolchinsky, R. Wyatt, M. Cayabyab, N. P. Gerard, C. Gerard, J. Sodroski, and H. Choe. 1999. Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell 96:667-676.
28. Fätkenheuer, G., A. L. Pozniak, M. A. Johnson, A. Plettenberg, S. Straszewski, A. I. Hoepelman, M. S. Sagg, F. D. Goebel, J. K. Rockstroh, B. J. Dezube, T. M. Jenkins, C. Medhurst, J. F. Sullivan, C. Ridgway, S. Abel, I. T. James, M. Youle, and E. van der Ryst. 2005. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat. Med. 11:1170-1172.
29. 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.
30. Gorny, M. K., K. Revesz, C. Williams, B. Volsky, M. K. Louder, C. A. Anyangwe, C. Krachmarov, S. C. Kayman, A. Pinter, A. Nadas, P. N. Nyambi, J. R. Mascola, and S. Zolla-Pazner. 2004. The v3 loop is accessible on the surface of most human immunodeficiency virus type 1 primary isolates and serves as a neutralization epitope. J. Virol. 78:2394-2404. (Pubitemid 38228932)
31. Gorny, M. K., C. Williams, B. Volsky, K. Revesz, S. Cohen, V. R. Polonis, W. J. Honnen, S. C. Kayman, C. Krachmarov, A. Pinter, and S. Zolla-Pazner. 2002. Human monoclonal antibodies specific for conformation-sensitive epitopes of V3 neutralize human immunodeficiency virus type 1 primary isolates from various clades. J. Virol. 76:9035-9045.
32. Gulick, R. M., Z. Su, C. Flexner, M. D. Hughes, P. R. Skolnik, T. J. Wilkin, R. Gross, A. Krambrink, E. Coakley, W. L. Greaves, A. Zolopa, R. Reichman, C. Godfrey, M. Hirsch, and D. R. Kuritzkes. 2007. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211. J. Infect. Dis. 196:304-312.
33. Hartley, O., P. J. Klasse, Q. J. Sattentau, and J. P. Moore. 2005. V3: HIV's switch-hitter. AIDS Res. Hum. Retrovir. 21:171-189.
34. Hoffman, T. L., and R. W. Doms. 1999. HIV-1 envelope determinants for cell tropism and chemokine receptor use. Mol. Membr. Biol. 16:57-65. (Pubitemid 29179338)
35. Hu, Q., K. B. Napier, J. O. Trent, Z. Wang, S. Taylor, G. E. Griffin, S. C. Peiper, and R. J. Shattock. 2005. Restricted variable residues in the C-terminal segment of HIV-1 V3 loop regulate the molecular anatomy of CCR5 utilization. J. Mol. Biol. 350:699-712. (Pubitemid 40848668)
36. Huang, C. C., S. N. Lam, P. Acharya, M. Tang, S. H. Xiang, S. S. Hussan, R. L. Stanfield, J. Robinson, J. Sodroski, I. A. Wilson, R. Wyatt, C. A. Bewley, and P. D. Kwong. 2007. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 317:1930-1934.
37. Huang, C. C., M. Tang, M. Y. Zhang, S. Majeed, E. Montabana, R. L. Stanfield, D. S. Dimitrov, B. Korber, J. Sodroski, I. A. Wilson, R. Wyatt, and P. D. Kwong. 2005. Structure of a V3-containing HIV-1 gp120 core. Science 310:1025-1028.
38. Hwang, S. S., T. J. Boyle, H. K. Lyerly, and B. R. Cullen. 1992. Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1. Science 257:535-537.
39. Javaherian, K., A. J. Langlois, G. J. LaRosa, A. T. Profy, D. P. Bolognesi, W. C. Herlihy, S. D. Putney, and T. J. Matthews. 1990. Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1. Science 250:1590-1593.
40. Johnson, W. E., J. Morgan, J. Reitter, B. A. Puffer, S. Czajak, R. W. Doms, and R. C. Desrosiers. 2002. A replication-competent, neutralization- sensitive variant of simian immunodeficiency virus lacking 100 amino acids of envelope. J. Virol. 76:2075-2086.
41. Kajumo, F., D. A. Thompson, Y. Guo, and T. Dragic. 2000. Entry of R5X4 and X4 human immunodeficiency virus type 1 strains is mediated by negatively charged and tyrosine residues in the amino-terminal domain and the second extracellular loop of CXCR4. Virology 271:240-247.
42. Koch, M., M. Pancera, P. D. Kwong, P. Kolchinsky, C. Grundner, L. Wang, W. A. Hendrickson, J. Sodroski, and R. Wyatt. 2003. Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition. Virology 313:387-400.
43. + cell depletion and progression to AIDS. Ann. Intern. Med. 118:681-688.
44. Koot, M., R. van Leeuwen, R. E. de Goede, I. P. Keet, S. Danner, J. K. Eeftinck Schattenkerk, P. Reiss, M. Tersmette, J. M. Lange, and H. Schuitemaker. 1999. Conversion rate towards a syncytium-inducing (SI) phenotype during different stages of human immunodeficiency virus type 1 infection and prognostic value of SI phenotype for survival after AIDS diagnosis. J. Infect. Dis. 179:254-258. (Pubitemid 29028366)
45. Krachmarov, C., S. C. Kayman, W. J. Honnen, O. Trochev, and A. Pinter. 2001. V3-specific polyclonal antibodies affinity purified from sera of infected humans effectively neutralize primary isolates of human immunodeficiency virus type 1. AIDS Res. Hum. Retrovir. 17:1737-1748. (Pubitemid 34114211)
46. Kuhmann, S. E., and O. Hartley. 2008. Targeting chemokine receptors in HIV: a status report. Annu. Rev. Pharmacol. Toxicol. 48:425-461.
47. Kuhmann, S. E., P. Pugagh, 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. 2004. Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. J. Virol. 78:2790-2805.
48. Kwong, P. D., R. Wyatt, J. Robinson, R. W. Sweet, J. Sodroski, and W. A. Hendrickson. 1998. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:648-659.
49. Laakso, M. M., F. H. Lee, B. Haggarty, C. Agrawal, K. M. Nolan, M. Biscone, J. Romano, A. P. Jordan, G. J. Leslie, E. G. Meissner, L. Su, J. A. Hoxie, and R. W. Doms. 2007. V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies. PLoS Pathog. 3:e117.
50. Lee, B., M. Sharron, C. Blanpain, B. J. Doranz, J. Vakili, P. Setoh, E. Berg, G. Liu, H. R. Guy, S. R. Durell, M. Parmentier, C. N. Chang, K. Price, M. Tsang, and R. W. Doms. 1999. Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function. J. Biol. Chem. 274:9617-9626. (Pubitemid 129517938)
51. Li, Y., B. Cleveland, I. Klots, B. Travis, B. A. Richardson, D. Anderson, D. Montefiori, P. Polacino, and S. L. Hu. 2008. Removal of a single N-linked glycan in human immunodeficiency virus type 1 gp120 results in an enhanced ability to induce neutralizing antibody responses. J. Virol. 82:638-651.
52. Li, Y., S. A. Migueles, B. Welcher, K. Svehla, A. Phogat, M. K. Louder, X. Wu, G. M. Shaw, M. Connors, R. T. Wyatt, and J. R. Mascola. 2007. Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat. Med. 13:1032-1034. (Pubitemid 47517505)
53. Lin, G., A. Bertolotti-Ciarlet, B. Haggarty, J. Romano, K. M. Nolan, G. J. Leslie, A. P. Jordan, C. C. Huang, P. D. Kwong, R. W. Doms, and J. A. Hoxie. 2007. Replication-competent variants of human immunodeficiency virus type 2 lacking the V3 loop exhibit resistance to chemokine receptor antagonists. J. Virol. 81:9956-9966. (Pubitemid 350067699)
54. 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.
55. Maeda, K., H. Nakata, Y. Koh, T. Miyakawa, H. Ogata, Y. Takaoka, S. Shibayama, K. Sagawa, D. Fukushima, J. Moravek, Y. Koyanagi, and H. Mitsuya. 2004. Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro. J. Virol. 78:8654-8662. (Pubitemid 39025131)
56. Marozsan, A. J., S. E. Kuhmann, T. Morgan, C. Herrera, E. Rivera-Troche, S. Xu, B. M. Baroudy, J. M. Strizki, and J. P. Moore. 2005. Generation and properties of a human immunodeficiency virus type 1 isolate resistant to the small molecule CCR5 inhibitor, SCH-417690 (SCH-D). Virology 338:182-199. (Pubitemid 40835936)
57. Meissner, E. G., K. M. Duus, F. Gao, X. F. Yu, and L. Su. 2004. Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor: role of the envelope. Virology 328:74-88.
58. Nichols, W. G., H. M. Steel, T. Bonny, K. Adkison, L. Curtis, J. Millard, K. Kabeya, and N. Clumeck. 2008. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob. Agents Chemother. 52:858-865.
59. Nolan, K. M., A. P. Jordan, and J. A. Hoxie. 2008. Effects of partial deletions within the human immunodeficiency virus type 1 V3 loop on coreceptor tropism and sensitivity to entry inhibitors. J. Virol. 82:664-673.
60. Ogert, R. A., L. Wojcik, P. Buontempo, R. Ralston, J. M. Strizki, and J. A. Howe. 2008. Mapping resistance to the CCR5 co-receptor antagonist vicriviroc using heterologous chimeric HIV-1 envelope genes reveals key determinants in the C2-V5 domain of gp120. Virology 373:387-399.
61. Pantophlet, R., and D. R. Burton. 2006. GP120: target for neutralizing HIV-1 antibodies. Annu. Rev. Immunol. 24:739-769.
62. Pfizer, Inc. 24 April 2007. Maraviroc tablets NDA 22-128. Antiviral Drugs Advisory Committee (AVDAC) briefing document. Pfizer, Inc., New York, NY. http://www.fda.gov/OHRMS/DOCKETS/AC/07/briefing/2007-4283b1-01-Pfizer.pdf.
63. Pugach, P., A. J. Marozsan, T. J. Ketas, E. L. Landes, J. P. Moore, and S. E. Kuhmann. 2007. HIV-1 clones resistant to a small molecule CCR5 inhibitor use the inhibitor-bound form of CCR5 for entry. Virology 361:212-228.
64. Richman, D. D., and S. A. Bozzette. 1994. The impact of the syncytium-inducing phenotype of human immunodeficiency virus on disease progression. J. Infect. Dis. 169:968-974. (Pubitemid 24303213)
65. Rizzuto, C., and J. Sodroski. 2000. Fine definition of a conserved CCR5-binding region on the human immunodeficiency virus type 1 glycoprotein 120. AIDS Res. Hum. Retrovir. 16:741-749. (Pubitemid 30327291)
66. Rizzuto, C. D., R. Wyatt, N. Hernandez-Ramos, Y. Sun, P. D. Kwong, W. A. Hendrickson, and J. Sodroski. 1998. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280:1949-1953.
67. Rucker, J., B. J. Doranz, A. L. Edinger, D. Long, J. F. Berson, and R. W. Doms. 1997. Cell-cell fusion assay to study role of chemokine receptors in human immunodeficiency virus type 1 entry. Methods Enzymol. 288:118-133. (Pubitemid 27443764)
68. Rucker, J., M. Samson, B. J. Doranz, F. Libert, J. F. Berson, Y. Yi, R. J. Smyth, R. G. Collman, C. C. Broder, G. Vassart, R. W. Doms, and M. Parmentier. 1996. Regions in β-chemokine receptors CCR5 and CCR2b that determine HIV-1 cofactor specificity. Cell 87:437-446.
69. Rusche, J. R., K. Javaherian, C. McDanal, J. Petro, D. L. Lynn, R. Grimaila, A. J. Langlois, R. C. Gallo, L. O. Arthur, P. J. Fischinger, D. P. Bolognesi, S. D. Putney, and T. J. Matthews. 1988. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc. Natl. Acad. Sci. USA 85:3198-3202. (Pubitemid 18138183)
70. Safarian, D., X. Carnec, F. Tsamis, F. Kajumo, and T. Dragic. 2006. An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry. Virology 352:477-484.
71. 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.
72. Sanders, R. W., L. Schiffner, A. Master, F. Kajumo, Y. Guo, T. Dragic, J. P. Moore, and J. M. Binley. 2000. Variable-loop-deleted variants of the human immunodeficiency virus type 1 envelope glycoprotein can be stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits. J. Virol. 74:5091-5100. (Pubitemid 30313848)
73. Saphire, E. O., P. W. Parren, R. Pantophlet, M. B. Zwick, G. M. Morris, P. M. Rudd, R. A. Dwek, R. L. Stanfield, D. R. Burton, and I. A. Wilson. 2001. Crystal structure of a neutralizing human IgG against HIV-1: a template for vaccine design. Science 293:1155-1159.
74. Scanlan, C. N., R. Pantophlet, M. R. Wormald, E. Ollmann Saphire, R. Stanfield, I. A. Wilson, H. Katinger, R. A. Dwek, P. M. Rudd, and D. R. Burton. 2002. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of α1→2 mannose residues on the outer face of gp120. J. Virol. 76:7306-7321.
75. Schuitemaker, H., M. Koot, N. A. Kootstra, M. W. Dercksen, R. E. Y. 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 populations. J. Virol. 66:1354-1360.
76. Seibert, C., W. Ying, S. Gavrilov, F. Tsamis, S. E. Kuhmann, A. Palani, J. R. Tagat, J. W. Clader, S. W. McCombie, B. M. Baroudy, S. O. Smith, T. Dragic, J. P. Moore, and T. P. Sakmar. 2006. Interaction of small molecule inhibitors of HIV-1 entry with CCR5. Virology 349:41-54.
77. Strizki, J. M., C. Tremblay, S. Xu, L. Wojcik, N. Wagner, W. Gonsiorek, R. W. Hipkin, C. C. Chou, C. Pugliese-Sivo, Y. Xiao, J. R. Tagat, K. Cox, T. Priestley, S. Sorota, W. Huang, M. Hirsch, G. R. Reyes, and B. M. Baroudy. 2005. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 49:4911-4919.
78. Suphaphiphat, P., A. Thitithanyanont, S. Paca-Uccaralertkun, M. Essex, and T. H. Lee. 2003. Effect of amino acid substitution of the V3 and bridging sheet residues in human immunodeficiency virus type 1 subtype C gp120 on CCR5 utilization. J. Virol. 77:3832-3837. (Pubitemid 36297302)
79. Trkola, A., 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. 2002. HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc. Natl. Acad. Sci. USA 99:395-400.
80. Tsamis, F., S. Gavrilov, F. Kajumo, C. Seibert, S. E. Kuhmann, T. Ketas, A. Trkola, A. Palani, J. W. Clader, J. R. Tagat, S. McCombie, B. M. 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. (Pubitemid 36460934)
81. Tsibris, A. M., and D. R. Kuritzkes. 2007. Chemokine antagonists as therapeutics: focus on HIV-1. Annu. Rev. Med. 58:445-459.
82. Tsibris, A. M., M. Sagar, R. M. Gulick, Z. Su, M. Hughes, W. Greaves, M. Subramanian, C. Flexner, F. Giguel, K. E. Leopold, E. Coakley, and D. R. Kuritzkes. 2008. In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject. J. Virol. 82:8210-8214.
83. van't Wout, A. B., N. A. Kootstra, G. A. Mulder-Kampinga, N. Albrecht-van Lent, H. J. Scherpbier, J. Veenstra, K. Boer, R. A. Coutinho, F. Miedema, and H. Schuitemaker. 1994. Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. J. Clin. Investig. 94:2060-2067.
84. Watson, C., S. Jenkinson, W. Kazmierski, and T. Kenakin. 2005. The CCR5 receptor-based mechanism of action of 873140, a potent allosteric noncompetitive HIV entry inhibitor. Mol. Pharmacol. 67:1268-1282.
85. Weissenhorn, W., A. Dessen, S. C. Harrison, J. J. Skehel, and D. C. Wiley. 1997. Atomic structure of the ectodomain from HIV-1 gp41. Nature 387: 426-430.
86. Westby, M., M. Lewis, J. Whitcomb, M. Youle, A. L. Pozniak, I. T. James, T. M. Jenkins, M. Perros, and E. van der Ryst. 2006. Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J. Virol. 80: 4909-4920.
87. Westby, M., C. Smith-Burchnell, J. Mori, M. Lewis, M. Mosley, M. Stockdale, P. Dorr, G. Ciaramella, and M. Perros. 2007. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. J. Virol. 81:2359-2371. (Pubitemid 46303353)
88. Westby, M., and E. van der Ryst. 2005. CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection. Antivir. Chem. Chemother. 16:339-354.
89. Wyatt, R., M. Thali, S. Tilley, A. Pinter, M. Posner, D. Ho, J. Robinson, and J. Sodroski. 1992. Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region. J. Virol. 66:6997-7004.
90. Zhou, T., L. Xu, B. Dey, A. J. Hessell, D. Van Ryk, S. H. Xiang, X. Yang, M. Y. Zhang, M. B. Zwick, J. Arthos, D. R. Burton, D. S. Dimitrov, J. Sodroski, R. Wyatt, G. J. Nabel, and P. D. Kwong. 2007. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445:732-737.
91. Zhu, T., H. Mo, N. Wang, D. S. Nam, Y. Cao, R. A. Koup, and D. D. Ho. 1993. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261:1179-1181.