A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity

Retrovirology

Volumn 12, Issue 1, 2015, Pages

  Garcia Perez, Javier ^b   Staropoli, Isabelle ^a   Azoulay, Stéphane ^c   Heinrich, Jean Thomas ^c   Cascajero, Almudena ^b   Colin, Philippe ^a,d   Lortat Jacob, Hugues ^e,f,g   Arenzana Seisdedos, Fernando ^a   Alcami, Jose ^b   Kellenberger, Esther ^c   Lagane, Bernard ^a  

^a INSTITUT PASTEUR   (France)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c UNIVERSITÉ DE STRASBOURG   (France)

^d UNIVERSITÉ PARIS DESCARTES   (France)

^e UNIV GRENOBLE ALPES   (France)

^f INSTITUT DE BIOLOGIE STRUCTURALE   (France)

^g CEA GRENOBLE   (France)

Author keywords

AIDS; Allosteric inhibitor; CCR5; CD4; gp120; HIV entry; HIV replication capacity; HIV 1; Maraviroc; Resistance

Indexed keywords

ALANINE; CD4 ANTIGEN; CHEMOKINE RECEPTOR CCR5; MARAVIROC; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CCR5 PROTEIN, HUMAN; CYCLOHEXANE DERIVATIVE; GLYCOPROTEIN GP 120; GP120 PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; MUTANT PROTEIN; PROTEIN BINDING; TRIAZOLE DERIVATIVE; VIRUS RECEPTOR;

ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; BINDING AFFINITY; CASE REPORT; CD4+ T LYMPHOCYTE; CELL FUSION; CLINICAL TRIAL (TOPIC); HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR DOCKING; NONHUMAN; PHENOTYPE; PROTEIN INTERACTION; RECEPTOR BINDING; SECOND EXTRACELLULAR LOOP; VIRUS ENVELOPE; VIRUS INFECTION; VIRUS INFECTIVITY; VIRUS MORPHOLOGY; VIRUS REPLICATION; DRUG EFFECTS; GENETICS; METABOLISM; MISSENSE MUTATION; VIRUS ENTRY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTI-HIV AGENTS; CYCLOHEXANES; DRUG RESISTANCE, VIRAL; HIV ENVELOPE PROTEIN GP120; HIV-1; HUMANS; MUTANT PROTEINS; MUTATION, MISSENSE; PROTEIN BINDING; RECEPTORS, CCR5; RECEPTORS, HIV; TRIAZOLES; VIRUS INTERNALIZATION; VIRUS REPLICATION;

EID: 84934925969     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/s12977-015-0177-1     Document Type: Article

References (78)

1. Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ et al (2014) International Union of Pharmacology. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev 66:1-79
2. Cormier EG, Dragic T (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
3. Huang CC, Tang M, Zhang MY, Majeed S, Montabana E, Stanfield RL et al (2005) Structure of a V3-containing HIV-1 gp120 core. Science 310:1025-1028
4. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA (1998) Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:648-659
5. Brelot A, Heveker N, Adema K, Hosie MJ, Willett B, Alizon M (1999) Effect of mutations in the second extracellular loop of CXCR4 on its utilization by human and feline immunodeficiency viruses. J Virol 73:2576-2586
6. Brower ET, Schon A, Klein JC, Freire E (2009) Binding thermodynamics of the N-terminal peptide of the CCR5 coreceptor to HIV-1 envelope glycoprotein gp120. Biochemistry 48:779-785
7. Cormier EG, Persuh M, Thompson DA, Lin SW, Sakmar TP, Olson WC et al (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
8. Lee B, Sharron M, Blanpain C, Doranz BJ, Vakili J, Setoh P et al (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
9. Huang CC, Lam SN, Acharya P, Tang M, Xiang SH, Hussan SS et al (2007) Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 317:1930-1934
10. Mkrtchyan SR, Markosyan RM, Eadon MT, Moore JP, Melikyan GB, Cohen FS (2005) Ternary complex formation of human immunodeficiency virus type 1 Env, CD4, and chemokine receptor captured as an intermediate of membrane fusion. J Virol 79:11161-11169
11. Haqqani AA, Tilton JC (2013) Entry inhibitors and their use in the treatment of HIV-1 infection. Antiviral Res 98:158-170
12. Moore JP, Kuritzkes DR (2009) A piece de resistance: how HIV-1 escapes small molecule CCR5 inhibitors. Curr Opin HIV AIDS 4:118-124
13. Garcia-Perez J, Rueda P, Alcami J, Rognan D, Arenzana-Seisdedos F, Lagane B et al (2011) Allosteric model of maraviroc binding to CC chemokine receptor 5 (CCR5). J Biol Chem 286:33409-33421
14. Garcia-Perez J, Rueda P, Staropoli I, Kellenberger E, Alcami J, Arenzana-Seisdedos F et al (2011) New insights into the mechanisms whereby low molecular weight CCR5 ligands inhibit HIV-1 infection. J Biol Chem 286:4978-4990
15. Tan Q, Zhu Y, Li J, Chen Z, Han GW, Kufareva I et al (2013) Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex. Science 341:1387-1390
16. Roche M, Jakobsen MR, Sterjovski J, Ellett A, Posta F, Lee B et al (2011) HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less-efficient mechanism of gp120-CCR5 engagement that attenuates macrophage tropism. J Virol 85:4330-4342
17. Roche M, Salimi H, Duncan R, Wilkinson BL, Chikere K, Moore MS et al (2013) A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. Retrovirology 10:43
18. Tilton JC, Wilen CB, Didigu CA, Sinha R, Harrison JE, Agrawal-Gamse C et al (2010) A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5. J Virol 84:10863-10876
19. Westby M, Smith-Burchnell C, Mori J, Lewis M, Mosley M, Stockdale M et al (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
20. Pugach P, Marozsan AJ, Ketas TJ, Landes EL, Moore JP, Kuhmann SE (2007) HIV-1 clones resistant to a small molecule CCR5 inhibitor use the inhibitor-bound form of CCR5 for entry. Virology 361:212-228
21. Berro R, Klasse PJ, Jakobsen MR, Gorry PR, Moore JP, Sanders RW (2012) V3 determinants of HIV-1 escape from the CCR5 inhibitors maraviroc and vicriviroc. Virology 427:158-165
22. Kuhmann SE, Pugach P, Kunstman KJ, Taylor J, Stanfield RL, Snyder A et al (2004) Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. J Virol 78:2790-2807
23. Ogert RA, Hou Y, Ba L, Wojcik L, Qiu P, Murgolo N et al (2010) Clinical resistance to vicriviroc through adaptive V3 loop mutations in HIV-1 subtype D gp120 that alter interactions with the N-terminus and ECL2 of CCR5. Virology 400:145-155
24. Tsibris AM, Sagar M, Gulick RM, Su Z, Hughes M, Greaves W et al (2008) In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject. J Virol 82:8210-8214
25. Anastassopoulou CG, Ketas TJ, Klasse PJ, Moore JP (2009) Resistance to CCR5 inhibitors caused by sequence changes in the fusion peptide of HIV-1 gp41. Proc Natl Acad Sci USA 106:5318-5323
26. Berro R, Sanders RW, Lu M, Klasse PJ, Moore JP (2009) Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry. PLoS Pathog 5:e1000548
27. Ratcliff AN, Shi W, Arts EJ (2013) HIV-1 resistance to maraviroc conferred by a CD4 binding site mutation in the envelope glycoprotein gp120. J Virol 87:923-934
28. Recordon-Pinson P, Raymond S, Bellecave P, Marcelin AG, Soulie C, Descamps D et al (2013) HIV-1 dynamics and coreceptor usage in Maraviroc-treated patients with ongoing replication. Antimicrob Agents Chemother 57:930-935
29. Putcharoen O, Lee SH, Henrich TJ, Hu Z, Vanichanan J, Coakley E et al (2012) HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug. J Virol 86:1119-1128
30. Tsibris AM, Hu Z, Paredes R, Leopold KE, Putcharoen O, Schure AL et al (2012) Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures. J Virol 86:6416-6426
31. Anastassopoulou CG, Marozsan AJ, Matet A, Snyder AD, Arts EJ, Kuhmann SE et al (2007) Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a fitness loss. PLoS Pathog 3:e79
32. Pfaff JM, Wilen CB, Harrison JE, Demarest JF, Lee B, Doms RW et al (2010) HIV-1 resistance to CCR5 antagonists associated with highly efficient use of CCR5 and altered tropism on primary CD4+ T cells. J Virol 84:6505-6514
33. Flynn JK, Paukovics G, Moore MS, Ellett A, Gray LR, Duncan R et al (2013) The magnitude of HIV-1 resistance to the CCR5 antagonist maraviroc may impart a differential alteration in HIV-1 tropism for macrophages and T-cell subsets. Virology 442:51-58
34. Chikere K, Chou T, Gorry PR, Lee B (2013) Affinofile profiling: how efficiency of CD4/CCR5 usage impacts the biological and pathogenic phenotype of HIV. Virology 435:81-91
35. Olson WC, Rabut GE, Nagashima KA, Tran DN, Anselma DJ, Monard SP et al (1999) Differential inhibition of human immunodeficiency virus type 1 fusion, gp120 binding, and CC-chemokine activity by monoclonal antibodies to CCR5. J Virol 73:4145-4155
36. Garcia-Perez J, Sanchez-Palomino S, Perez-Olmeda M, Fernandez B, Alcami J (2007) A new strategy based on recombinant viruses as a tool for assessing drug susceptibility of human immunodeficiency virus type 1. J Med Virol 79:127-137
37. Heredia A, Latinovic O, Gallo RC, Melikyan G, Reitz M, Le N et al (2008) Reduction of CCR5 with low-dose rapamycin enhances the antiviral activity of vicriviroc against both sensitive and drug-resistant HIV-1. Proc Natl Acad Sci USA 105:20476-20481
38. Parker ZF, Iyer SS, Wilen CB, Parrish NF, Chikere KC, Lee FH et al (2013) Transmitted/founder and chronic HIV-1 envelope proteins are distinguished by differential utilization of CCR5. J Virol 87:2401-2411
39. Pugach P, Ray N, Klasse PJ, Ketas TJ, Michael E, Doms RW et al (2009) Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities. Virology 387:296-302
40. Roche M, Jakobsen MR, Ellett A, Salimiseyedabad H, Jubb B, Westby M et al (2011) HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry. Retrovirology 8:89
41. Healey D, Dianda L, Moore JP, McDougal JS, Moore MJ, Estess P et al (1990) Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4 + cells from virus binding. J Exp Med 172:1233-1242
42. Xu XH, Wen Z, Brownlow WJ (2013) Ultrasensitive analysis of binding affinity of HIV receptor and neutralizing antibody using solution-phase electrochemiluminescence assay. J Electroanal Chem (Lausanne Switz) 688:53-60
43. Dunfee RL, Thomas ER, Gorry PR, Wang J, Taylor J, Kunstman K et al (2006) The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci USA 103:15160-15165
44. Zhang W, Godillot AP, Wyatt R, Sodroski J, Chaiken I (2001) Antibody 17b binding at the coreceptor site weakens the kinetics of the interaction of envelope glycoprotein gp120 with CD4. Biochemistry 40:1662-1670
45. Sterjovski J, Churchill MJ, Roche M, Ellett A, Farrugia W, Wesselingh SL et al (2011) CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity. Virology 410:418-428
46. Colin P, Benureau Y, Staropoli I, Wang Y, Gonzalez N, Alcami J et al (2013) HIV-1 exploits CCR5 conformational heterogeneity to escape inhibition by chemokines. Proc Natl Acad Sci USA 110:9475-9480
47. Connell BJ, Baleux F, Coic YM, Clayette P, Bonnaffe D, Lortat-Jacob H (2012) A synthetic heparan sulfate-mimetic peptide conjugated to a mini CD4 displays very high anti- HIV-1 activity independently of coreceptor usage. Chem Biol 19:131-139
48. Doranz BJ, Baik SS, Doms RW (1999) Use of a gp120 binding assay to dissect the requirements and kinetics of human immunodeficiency virus fusion events. J Virol 73:10346-10358
49. Berro R, Klasse PJ, Lascano D, Flegler A, Nagashima KA, Sanders RW et al (2011) Multiple CCR5 conformations on the cell surface are used differentially by human immunodeficiency viruses resistant or sensitive to CCR5 inhibitors. J Virol 85:8227-8240
50. Flegler AJ, Cianci GC, Hope TJ (2014) CCR5 conformations are dynamic and modulated by localization, trafficking and g protein association. PLoS One 9:e89056
51. Xiang SH, Wang L, Abreu M, Huang CC, Kwong PD, Rosenberg E et al (2003) Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains. Virology 315:124-134
52. Julien JP, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC et al (2013) Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342:1477-1483
53. Kwon JC, Kim SH, Park SH, Choi SM, Lee DG, Choi JH et al (2011) Molecular epidemiologic analysis of methicillin-resistant Staphylococcus aureus isolates from bacteremia and nasal colonization at 10 intensive care units: multicenter prospective study in Korea. J Korean Med Sci 26:604-611
54. Pancera M, Majeed S, Ban YE, Chen L, Huang CC, Kong L et al (2010) Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. Proc Natl Acad Sci USA 107:1166-1171
55. Cavrois M, De Noronha C, Greene WC (2002) A sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytes. Nat Biotechnol 20:1151-1154
56. Melikyan GB, Platt EJ, Kabat D (2007) The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment. Retrovirology 4:55
57. Tamamis P, Floudas CA (2014) Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop. PLoS One 9:e95767
58. Lagane B, Garcia-Perez J, Kellenberger E (2013) Modeling the allosteric modulation of CCR5 function by Maraviroc. Drug Discov Today Technol 10:e297-e305
59. Marozsan AJ, Moore DM, Lobritz MA, Fraundorf E, Abraha A, Reeves JD et al (2005) Differences in the fitness of two diverse wild-type human immunodeficiency virus type 1 isolates are related to the efficiency of cell binding and entry. J Virol 79:7121-7134
60. Reeves JD, Gallo SA, Ahmad N, Miamidian JL, Harvey PE, Sharron M et al (2002) Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci USA 99:16249-16254
61. Agrawal-Gamse C, Lee FH, Haggarty B, Jordan AP, Yi Y, Lee B et al (2009) Adaptive mutations in a human immunodeficiency virus type 1 envelope protein with a truncated V3 loop restore function by improving interactions with CD4. J Virol 83:11005-11015
62. Platt EJ, Durnin JP, Kabat D (2005) Kinetic factors control efficiencies of cell entry, efficacies of entry inhibitors, and mechanisms of adaptation of human immunodeficiency virus. J Virol 79:4347-4356
63. Blanpain C, Vanderwinden JM, Cihak J, Wittamer V, Le Poul E, Issafras H et al (2002) Multiple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies. Mol Biol Cell 13:723-737
64. Berro R, Yasmeen A, Abrol R, Trzaskowski B, Abi-Habib S, Grunbeck A et al (2013) Use of G-protein-coupled and -uncoupled CCR5 receptors by CCR5 inhibitor-resistant and -sensitive human immunodeficiency virus type 1 variants. J Virol 87:6569-6581
65. Alves ID, Salamon Z, Hruby VJ, Tollin G (2005) Ligand modulation of lateral segregation of a G-protein-coupled receptor into lipid microdomains in sphingomyelin/phosphatidylcholine solid-supported bilayers. Biochemistry 44:9168-9178
66. Mondal S, Khelashvili G, Johner N, Weinstein H (2014) How the dynamic properties and functional mechanisms of GPCRs are modulated by their coupling to the membrane environment. Adv Exp Med Biol 796:55-74
67. Liu Y, Belkina NV, Shaw S (2009) HIV infection of T cells: actin-in and actin-out. Sci Signal 2:pe23
68. Harmon B, Campbell N, Ratner L (2010) Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step. PLoS Pathog 6:e1000956
69. Abrol R, Trzaskowski B, Goddard WA, 3rd, Nesterov A, Olave I, Irons C (2014) Ligand- and mutation-induced conformational selection in the CCR5 chemokine G protein-coupled receptor. In: Proceedings of the National Academy of Sciences of the United States of America
70. Laakso MM, Lee FH, Haggarty B, Agrawal C, Nolan KM, Biscone M et al (2007) V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies. PLoS Pathog 3:e117
71. Lin G, Bertolotti-Ciarlet A, Haggarty B, Romano J, Nolan KM, Leslie GJ et al (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
72. Nolan KM, Jordan AP, Hoxie JA (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
73. Johnston SH, Lobritz MA, Nguyen S, Lassen K, Delair S, Posta F et al (2009) A quantitative affinity-profiling system that reveals distinct CD4/CCR5 usage patterns among human immunodeficiency virus type 1 and simian immunodeficiency virus strains. J Virol 83:11016-11026
74. Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099-3108
75. Lagane B, Ballet S, Planchenault T, Balabanian K, Le Poul E, Blanpain C et al (2005) Mutation of the DRY motif reveals different structural requirements for the CC chemokine receptor 5-mediated signaling and receptor endocytosis. Mol Pharmacol 67:1966-1976
76. Jin J, Colin P, Staropoli I, Lima-Fernandes E, Ferret C, Demir A et al (2014) Targeting spare CC chemokine receptor 5 (CCR5) as a principle to inhibit HIV-1 entry. J Biol Chem 289:19042-19052
77. Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W et al (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24:1999-2012
78. Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V et al (2010) Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330:1066-1071