Chemokine receptors: Emerging opportunities for new anti-HIV therapies

Expert Opinion on Therapeutic Targets

Volumn 5, Issue 3, 2001, Pages 303-326

  Agrawal, Lokesh ^a   Alkhatib, Ghalib ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

32; CCR5; chemokine receptor; chemokines; co receptor; co receptor drugs; co receptor based therapy; CXCR4; entry inhibitors; fusion inhibitors; HIV entry inhibitors; HIV 1; human immunodeficiency virus; inhibitors; major co receptors; minor co receptors; polymorphism

Indexed keywords

EID: 0011770673     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.5.3.303     Document Type: Review

References (198)

1. The Durban Declaration. Nature (2000) 406(6791): 15-16.
2. CARR A, COOPER DA: Adverse effects of antiretroviral therapy. Lancet (2000) 356 (9239): 1423-1430.
3. FINZI D, HERMANKOVA M, PIERSON T et al.: Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science (1997) 278(5341): 1295-1300.
4. POMERANTZ RJ: HIV patients receiving HAART therapy can still transmit the virus. Highly active antiretroviral chemotherapy. Am. Fam. Physician (1999) 59(10):2855.
5. ZLOTNIK A, YOSHIE O: Chemokines: a new classification system and their role in immunity. Immunity (2000) 12:121-127.
6. COCCHI F, DEVICO AL, GARZINODEMO A et al: Identification of RANTES, MIP-1 oc, and MIP-1 p as the major HIV-suppressive factors produced by CD8(+) T cells. Science (1995) 270:1811-1815.
7. FENG Y, BRODER CC, KENNEDY PE et al: HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science (1996) 272:872-877.
8. ALKHATIB G, COMBADIERE C, BRODER CC et al.: CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science (1996) 272 (5270): 1955-1958.
9. CHOE H, FARZAN M, SUN Y et al: The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell (1996) 85 (7):1135-1148.
10. DENG H, LIU R, ELLMEIER W et al: Identification of a major co-receptor for primary isolates of HIV-1 [see comments]. Nature (1996) 381(6584):661-666.
11. DORANZ BJ, RUCKER J, YI Y et al.: 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 (1996) 85(7): 1149-1158.
12. DRAGIC T, LITWIN V, ALLAWAY GP et al: HIV-1 entry into CD4(+) cells is mediated by the chemokine receptor CC-CKR-5. Nature (1996) 381:667-673.
13. LIU R, PAXTON WA, CHOE S et al: Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell (1996) 86(3):367-377.
14. SAMSON M, LIBERT F, DORANZ BJ et al: Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene [see comments]. Nature (1996) 382(6593):722-725.
15. BERGER EA, MURPHY PM, FARBER JM: Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Ann. Rev. Immunology (1999) 17:657-700.
16. NUSSBAUM O, BRODER CC, BERGER EA: Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J. Virol. (1994) 68:5411-5422.
17. BERGER EA, DOMS RW, FENYO EM et al: A new classification for HIV-1 [letter]. Nature (1998) 391 (6664):240.
18. ALKHATIB G, BERGER EA, MURPHY PM et al.: Determinants of HIV-1 coreceptor function on CC chemokine receptor 3. Importance of both extracellular and transmembrane/cytoplasmic regions. J. Biol. Chem. (1997) 272(33):20420-20426.
19. RUCKER J, EDINGER AL, SHARRON M et al.: Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses. J. Virol. (1997) 71(12):8999-9007.
20. LIAO F, ALKHATIB G, PEDEN KW et al: STRL33, A novel chemokine receptorlike protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J. Exp. Med. (1997) 185(11):2015-2023.
21. DENG HK, UNUTMAZ D, KEWALRAMANI VN et al: Expression cloning of new receptors used by simian and human immunodeficiency viruses [see comments]. Nature (1997) 388(6639):296-300.
22. CHOE H, FARZAN M, KONKEL M et al: The orphan seven-transmembrane receptor apj supports the entry of primary T-cell-line-tropic and dualtropic human immunodeficiency virus type 1. J. Virol. (1998) 72 (7) :6113-6118.
23. EDINGER AL, HOFFMAN TL, SHARRON M et al: An orphan seven-transmembrane domain receptor expressed widely in the brain functions as a coreceptor for human immunodeficiency virus type 1 and simian immunodeficiency virus. J. Virol. (1998) 72(10):7934-7940.
24. SHARRON M, POHLMANN S, PRICE K et al: Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes. Blood (2000) 96(1):41-49.
25. SIMMONS G, REEVES JD, HIBBITTS S et al: Co-receptor use by HIV and inhibition of HIV infection by chemokine receptor ligands.[In Process Citation]. Immunol Rev. (2000) 177:112-126.
26. BERGER EA: HIV entry and tropism: the chemokine receptor connection. AIDS (1997) 11(Suppl. A):S3-S16.
27. LAPHAM CK, OUYANG J, CHANDRASEKHAR B et al: Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines [see comments]. Science (1996) 274 (5287) :602-605.
28. UGOLINI S, MOULARD M, MONDOR I et al: HIV-1 gp 120 induces an association between CD4 and the chemokine receptor CXCR4. J. Immunol. (1997) 159(6):3000-3008.
29. XIAO X, WU L, STANTCHEV TS et al.: Constitutive cell surface association between CD4 and CCR5. Proc. Natl. Acad. Sci. USA (1999) 96(13) :7496-7501.
30. PLATT EJ, WEHRLY K, KUHMANN SE et al: Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J. Virol. (1998) 72(4):2855-2864.
31. KUHMANN SE, PLATT EJ, KOZAK SL et al: Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1. J. Virol. (2000) 74(15):7005-7015.
32. DIMITROV DS, NORWOOD D, STANTCHEV TS et al: A mechanism of resistance to HIV-1 entry: inefficient interactions of CXCR4 with CD4 and gp 120 in macrophages. Virology (1999) 259(1): 1-6.
33. WU L, GERARD NP, WYATT R et al: CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature (1996) 384(6605):179-183.
34. TRKOLA A, DRAGIC T, ARTHOS J et al.: CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature (1996) 384(6605):184-187.
35. ALKHATIB G, LOCATI M, KENNEDY PE et al.: HIV-1 coreceptor activity of CCR5 and its inhibition by chemokines: independence from G protein signaling and importance of coreceptor downmodulation. Virology (1997) 234(2):340-348.
36. DORANZ BJ, LU ZH, RUCKER J et al.: Two distinct CCR5 domains can mediate coreceptor usage by human immunodeficiency virus type 1. J. Virol. (1997) 71(9):6305-6314.
37. ATCHIS ON R E, GOS LING J, MONTECLARO FS et al.: Multiple extracellular elements of CCR5 and HIV-1 entry: dissociation from response to chemokines. Science (1996) 274(5294):1924-1926.
38. GOSLING J, MONTECLARO FS, AT C H I S O N R E et al.: Molecular uncoupling of C-C chemokine receptor 5-induced chemotaxis and signal transduction from HIV-1 coreceptor activity. Proc. Natl. Acad. Sci. USA (1997) 94(10):5061-5066.
39. LU Z, BERSON J F, CHEN Y et al.: Evolution of HIV-1 coreceptor usage through interactions with distinct CCR5 and CXCR4 domains. Proc. Natl. Acad. Sci. USA (1997) 94(12):6426-6431.
40. RUCKER J, SAMSON M, DORANZ BJ et al.: Regions in beta-chemokine receptors CCR5 and CCR2b that determine HIV-1 cofactor specificity. Cell (1996) 87(3):437-446.
41. DRAGIC T, TRKOLA A, LIN SW et al.: Amino-terminal substitutions in the CCR5 coreceptor impair gp120 binding and human immunodeficiency virus type 1 entry. J. Virol. (1998) 72(1):279-285.
42. PICARD L, SIMMONS G, POWER CA et al.: Multiple extracellular domains of CCR-5 contribute to human immunodeficiency virus type 1 entry and fusion. J. Virol. (1997) 71(7):5003-5011.
43. ZHANG YJ, DRAGIC T, CAO Y et al.: Use of coreceptors other than CCR5 by non-syncytium-inducing adult and pediatric isolates of human immunodeficiency virus type 1 is rare in vitro. J. Virol. (1998) 72(11):9337-9344.
44. ZHANG L, HE T, HUANG Y et al: Chemokine coreceptor usage by diverse primary isolates of human immunodeficiency virus type 1. J. Virol (1998) 72(11):9307-9312.
45. BAZAN HA, ALKHATIB G, BRODER CC et al: Patterns of CCR5, CXCR4, and CCR3 usage by envelope glycoproteins from human immunodeficiency virus typetype 1 primary isolates. J.Virol (1998) 72(5):4485-4491.
46. HE J, CHEN Y, FARZAN M et al: CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature (1997) 385 (6617):645-649.
47. SOL N, FERCHAL F, BRAUN J et al.: Usage of the coreceptors CCR-5, CCR-3, and CXCR-4 by primary and cell line-adapted human immunodeficiency virus type 2. J. Virol. (1997) 71(11):8237-8244.
48. SALLUSTO F, MACKAY CR, LANZAVECCHIA A: Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science (1997) 277(5334):2 005-200 7.
49. GHORPADE A, XIA MQ, HYMAN BT et al.: Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia. J. Virol. (1998) 72 (4):3351-3361.
50. STRUYF S, PROOST P, SCHOLS D et al: CD26/dipeptidyl-peptidase IV down-regulates the eosinophil chemotactic potency, but not the anti-HIV activity of human eotaxin by affecting its interaction with CC chemokine receptor 3. J. Immunol. (1999) 162 (8):4903-4909.
51. SABROE I, PECK MJ, VAN KEULEN BJ et al: A small molecule antagonist of chemokine receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. J. Biol. Chem. (2000) 275(34):25985-25992.
52. ZHANG Y, LOU B, LAL RB et al.: Use of inhibitors to evaluate coreceptor usage by simian and simian/human immunodeficiency viruses and human immunodeficiency virus type 2 in primary cells. J. Virol. (2000) 74(15):6893-6910.
53. SMITH MW, DEAN M, CARRINGTON M et al: Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. Science (1997) 277(5328):959-965.
54. LEE B, DORANZ BJ, RANA S et al.: Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4. J. Virol. (1998) 72(9):7450-7458.
55. MELLADO M, RODRIGUEZ-FRADE JM, VILA-CORO A et al: Chemokine control of HIV-1 infection. Nature (1999) 400:723-724.
56. LEE S, TIFFANY HL, KING L et al: CCR8 on human thymocytes functions as a human immunodeficiency virus type 1 coreceptor. J. Virol. (2000) 74 (15) :6946-6952.
57. AGRAWAL L, HE Y, ALKHATIB G: Analysis of CC chemokine receptor 4 (CCR4) coreceptor activity in peripheral blood mononuclear cells (PBMCs) and its inhibition by macrophage-derived chemokine (MDC). Submitted (2001).
58. COTA M, MENGOZZI M, VICENZI E et al: Selective inhibition of HIV replication in primary macrophages but not T lymphocytes by macrophage-derived chemokine. Proc. Natl. Acad. Sci. USA (2000) 97(16):9162-9167.
59. ZHANG YJ, MOORE JP: Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry? J. Virol. (1999) 73(4):3443-3448.
60. DEAN M, CARRINGTON M, WINKLER C et al: 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 [see comments] [published erratum appears in Science 1996 Nov 15;274(5290):1069]. Science (1996) 273(5283): 1856-1862.
61. HUANG Y, PAXTON WA, WOLINSKY SM et al: The role of a mutant CCR5 allele in HIV-1 transmission and disease progression [see comments]. Nature Med. (1996) 2(11): 1240-1243.
62. ZIMMERMAN PA, BUCKLER-WHITE A, ALKHATIB G et al: Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk. Mol Med. (1997) 3(1):23-36.
63. YI Y, RANA S, TURNER JD et al: CXCR-4 is expressed by primary macrophages and supports CCR5-independent infection by dual-tropic but not T-tropic isolates of human immunodeficiency virus type 1. J. Virol. (1998) 72(1):772-777.
64. WINKLER C, MODI W, SMITH MW et al: Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC) [see comments]. Science (1998) 279(5349):389-393.
65. KOSTRIKIS LG, HUANG Y, MOORE JP et al: A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nature Med. (1998) 4 (3): 350-353.
66. MUMMIDI S, AHUJA SS, MCDANIEL BL et al: The human CC chemokine receptor 5 (CCR5) gene. Multiple transcripts with 5'-end heterogeneity, dual promoter usage, and evidence for polymorphisms within the regulatory regions and noncoding exons. J. Biol. Chem. (1997) 272(49):30662-30671.
67. MUMMIDI S, AHUJA SS, GONZALEZ E et al: Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression. Nature Med. (1998) 4(7):786-793.
68. LUKACS NW, TEKKANAT KK: Role of chemokines in asthmatic airway inflammation.[In Process Citation]. Immunol. Rev. (2000) 177:21-30.
69. BAGGIOLINI M: Reflections on chemokines. [In Process Citation]. Immunol. Rev. (2000) 177:5-7.
70. KELNER GS, KENNEDY J, BACON KB et al: Lymphotactin: a cytokine that represents a new class of chemokine. Science (1994) 266(5189):1395-1399.
71. BAZAN JF, BACON KB, HARDIMAN G et al.: A new class of membrane-bound chemokine with a CX3C motif. Nature (1997) 385(6617):640-644.
72. AMARA A, GALL SL, SCHWARTZ O et al: HIV coreceptor downregulation as antiviral principle: SDF-1alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J. Exp. Med. (1997) 186(1): 139-146.
73. OBERLIN E, AMARA A, BACHELERIE F et al: The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature (1996) 382 (6594):833-835.
74. BLEUL CC, FARZAN M, CHOE H et al: The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature (1996) 382 (6594):829-833.
75. SIGNORET N, OLDRIDGE J, PELCHEN-MATTHEWS A et al: Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4. J. Cell Biol. (1997) 139(3):651-664.
76. BLANPAIN C, MIGEOTTE I, LEE B et al: CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. Blood (1999) 94(6):1899-1905.
77. BLAIR WS, LIN PF, MEANWELL NA et al: HIV-1 entry-an expanding portal for drug discovery. Drug Discov. Today (2000) 5(5): 183-194.
78. D'SOUZA MP, CAIRNS JS, PLAEGER SF: Current evidence and future directions for targeting HIV entry: therapeutic and prophylactic strategies. JAMA (2000) 284(2):215-222.
79. ALLAWAY GP, DAVIS-BRUNO KL, BEAUDRY GA et al.: Expression and characterization of CD4-IgG2, a novel he te rote tram er that neutralizes primary HIV type 1 isolates. AIDS Res. Human Retroviruses (1995) 11 (5):533-5 39.
80. TRKOLA A, KETAS T, KEWALRAMANI VN et al: Neutralization sensitivity of human immunodeficiency virus type 1 primary isolates to antibodies and CD4-based reagents is independent of coreceptor usage. J. Virol. (1998) 72 (3): 1876-1885.
81. BABA M, NISHIMURA O, KANZAKI N et al: A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. USA (1999) 96(10):5698-5703.
82. DRAGIC T, TRKOLA A, THOMPSON DA et al: A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc. Natl. Acad Sci. USA (2000) 97(10) :5639-5644.
83. SHIRAISHI M, ARAMAKI Y, SETO M et al: Discovery of novel, potent, and selective small-molecule CCR5 antagonists as anti-HIV-1 agents: synthesis and biological evaluation of anilide derivatives with a quaternary ammonium moiety. J. Med. Chem. (2000) 43(10):2049-2063.
84. REYES G: Development of CCR5 antagonists as a new class of anti-HIV Therapeutic. 8th Conference on Retroviruses and Opportunistic Infections (2001) Abstract L1 1
85. TRKOLA A, KETAS TJ, NAGASHIMA KA et al: Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J. Virol. (2001) 75(2):579-588.
86. OLSON WC, BURTON DR: Fusion Inhibitor PRO 140 reduces HIV burden in mouse model. 14th International Conference on Antiviral Research (2001).
87. SIMMONS G, CLAPHAM PR, PICARD L et al: Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science (1997) 276(5310) :2 76-279.
88. MACK M, LUCKOW B, NELSON PJ et al: Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity. J. Exp. Med. (1998) 187(8): 1215-1224.
89. MOSIER DE, PICCHIO GR, GULIZIA RJ et al: 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. (1999) 73(5):3544-3550.
90. ELSNER J, MACK M, BRUHL H et al.: Differential activation of CC chemokine receptors by AOP-RANTES. J. Biol. Chem. (2000) 275(11):7787-7794.
91. DE CLERCQ E, YAMAMOTO N, PAUWELS R et al: 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 (1992) 89(12):5286-5290.
92. SCHOLS D, ESTE JA, HENSON G et al.: Bicyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor fusin/CXCR-4. Antiviral Res. (1997) 35(3): 147-156.
93. DONZELLA GA, SCHOLS D, LIN SW et al: AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nature Med. (1998) 4(1):72-77.
94. LABROSSE B, BRELOT A, HEVEKER N et al: Determinants for sensitivity of human immunodeficiency virus coreceptor CXCR4 to the bicyclam AMD3100. J. Virol. (1998) 72(8):6381-6388.
95. DATEMA R, RABIN L, HINCENBERGS M et al: Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry. Antimicrob. Agents Chemother. (1996) 40(3) :750-754.
96. DE VREESE K, REYMEN D, GRIFFIN P et al: The bicyclams, a new class of potent human immunodeficiency virus inhibitors, block viral entry after binding. Antiviral Res. (1996) 29(2-3):209-219.
97. DE VREESE K, KOFLER-MONGOLD V, LEUTGEB C et al: The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication. J. Virol. (1996) 70(2):689-696.
98. DE VREESE K, VAN NERUM I, VERMEIRE K et al: Sensitivity of human immunodeficiency virus to bicyclam derivatives is influenced by the three-dimensional structure of gp120. Antimicrob. Agents Chemother. (1997) 41(12):2616-2620.
99. ESTE JA, CABRERA C, BLANCO J et al: Shift of clinical human immunodeficiency virus type 1 isolates from X4 to R5 and prevention of emergence of the syncytium-inducing phenotype by blockade of CXCR4. J. Virol. (1999) 73(7):5577-5585.
100. HENDRIX CW, FLEXNER C, MACFARLAND RT et al: Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob. Agents Chemother. (2000) 44 (6): 1667-1673.
101. MACFARLAND R, YASUDA N, WITVROUW M et al: An orally bioavailable CXCR4 antagonist for inhibition of HIV replication. Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (2000) Abstract 1845.
102. BRIDGER GJ, SKERLJ RT, PADMANABHAN S et al: Synthesis and structure-activity relationships of phenyleneb is(methylene)-l inked bis-azamacrocycles that inhibit HIV-1 and HIV-2 replication by antagonism of the chemokine receptor CXCR4. J. Med. Chem. (1999) 42(19):3971-3981.
103. BOSHOFF C, ENDO Y, COLLINS PD et al: Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines [see comments]. Science (1997) 278(5336):2 90-2 94.
104. KLEDAL TN, ROSENKILDE MM, COULIN F et al: A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science (1997) 277(5332): 1656-1659.
105. DORE GJ, GRULICH A, LAW MG et al: Kaposi's sarcoma and protection from AIDS dementia complex. AIDS (1998) 12(17):2354-2355.
106. LIESTAEL K, GOPLEN AK, DUNLOP O et al: Kaposi's sarcoma and protection from HIV dementia [letter; comment]. Science (1998) 280(5362):361-362.
107. HIBBITTS S, REEVES JD, SIMMONS G et al: Coreceptor ligand inhibition of fetal brain cell infection by HIV type 1. AIDS Res. Hum. Retroviruses (1999) 15(11) :989-1000.
108. NAGASHIMA KA, THOMPSON DA, ROSENFIELD SI et al: Human immunodeficiency virus type 1 entry inhibitors pro 542 and T-20 are potently synergistic in blocking virus-cell and cell-cell fusion. J. Infect. Dis. (2001) 183(7):1121-1125.
109. OLSON WC, THOMPSON DA, and NAGASHIMA KA et al.: Potent, synergistic inhibition of HIV-1 by combination of the viral entry inhibitors PRO 542, PRO 140, and T-20. Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (2000) Abstract 549.
110. TREMBLAY CL, KOLLMANN C, GIGUEL F et al: In vitro synergy observed between the fusion inhibitors T-20 and a CCR5 inhibitor TAK-779. Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (2000) Abstract 1164.
111. PICCHIO G, SABBE R, NEAL NEA: Coreceptor trap therapy: combination of CCR5 and CXCR4 inhibitors blocks human immunodeficiency virus type 1 infection in vivo. 8th Conference on Retroviruses and Opportunistic Infections (2001) Abstract 311.
112. BAI X, CHEN JD, YANG AG et al: Genetic co-inactivation of macrophage-and T-tropic HIV-1 chemokine coreceptors CCR-5 and CXCR-4 by intrakines. Gene Ther. (1998) 5(7):984-994.
113. YANG AG, BAI X, HUANG XF et al.: Phenotypic knockout of HIV type 1 chemokine coreceptor CCR-5 by intrakines as potential therapeutic approach for HIV-1 infection. Proc. Natl Acad. Sci. USA (1997) 94(21):11567-11572.
114. BENKIRANE M, JIN DY, CHUN RF et al.: Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5delta32. J. Biol. Chem. (1997) 272(49):3060 3-30606.
115. VERANI A, PESENTI E, POLO S et al.: CXCR4 is a functional coreceptor for infection of human macrophages by CXCR4-dependent primary HIV-1 isolates. J. Immunol. (1998) 161(5):2084-2088.
116. SIMMONS G, REEVES JD, MCKNIGHT A et al: CXCR4 as a functional coreceptor for human immunodeficiency virus type 1 infection of primary macrophages. J. Virol (1998) 72(10) :8453-8457.
117. BLEUL CC, WU L, HOXIE JA et al: The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes [see comments]. Proc. Natl. Acad. Sci. USA (1997) 94(5):1925-1930.
118. LEE B, SHARRON M, MONTANER LJ et al: Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc. Natl. Acad. Sci. USA (1999) 96(9):5215-5220.
119. MICHAEL NL, NELSON JA, KEWALRAMANI VN et al: Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32. J. Virol (1998) 72(7):6040-6047.
120. MARSHALL E, HOWELL AH, POWLES R et al: Clinical effects of human macrophage inflammatory protein-1 alpha MIP-1 alpha (LD78) administration to humans: a Phase I study in cancer patients and normal healthy volunteers with the genetically engineered variant, BB-10010. Eur. J. Cancer (1998) 34(7): 1023-1029.
121. CLEMONS MJ, MARSHALL E, DURIG J et al: A randomized phase-II study of BB-10010 (macrophage inflammatory protein-1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy. Blood (1998) 92(5): 1532-1540.
122. O'BRIEN SJ, MOORE JP: The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol. Rev. (2000) 177:99-111.
123. SATO N, KUZIEL WA, MELBY PC et al: Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in C C chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. J. Immunol. (1999) 163(10):5519-5525.
124. ZHOU Y, KURIHARA T, RYSECK RP et al: Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor. J. Immunol. (1998) 160(8):4018-4025.
125. HUFFNAGLE GB, MCNEIL LK, MCDONALD RA et al: Cutting edge: Role of C-C chemokine receptor 5 in organ-specific and innate immunity to Cryptococcus neoformans. J. Immunol. (1999) 163(9): 4642-4646.
126. PHILPOTT S, WEISER B, ANASTOS K et al: Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy. J. Clin. Invest. (2001) 107(4):431-438.
127. DE RODA HUSMAN AM, VAN RIJ RP, BLAAK H et al: Adaptation to promiscuous usage of chemokine receptors is not a prerequisite for human immunodeficiency virus type 1 disease progression. J. Infect. Dis. (1999) 180(4): 1106-1115.
128. SCHOLS D, ESTE JA, CABRERA C et al: T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1 alpha contains mutations in the envelope gp 120 but does not show a switch in coreceptor use. J. Virol. (1998) 72(5):4032-4037.
129. ZOU YR, KOTTMANN AH, KURODA M et al: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature (1998) 393(6685): 595-599.
130. TACHIBANA K, HIROTA S, IIZASA H et al: The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature (1998) 393 (6685): 591-594.
131. TRKOLA A, GORDON C, MATTHEWS J et al: 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. (1999) 73(8): 6370-6 379.
132. KINTER A, CATANZARO A, MONACO J et al: 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 (1998) 95(20):11880-11885.
133. WANG ZX, BERSON JF, ZHANG TY et al: CXCR4 sequences involved in coreceptor determination of human immunodeficiency virus type-1 tropism. Unmasking of activity with M-tropic Env glycoproteins. J. Biol. Chem. (1998) 273(24):15007-15015.
134. CHABOT DJ, BRODER CC: Substitutions in a homologous region of extracellular loop 2 of CXCR4 and CCR5 alter coreceptor activities for HIV-1 membrane fusion and virus entry [In Process Citation]. J. Biol. Chem. (2000) 275(31):23774-23782.
135. CHABOT DJ, CHEN H, DIMITROV DS et al.: N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus typetype 1 isolates. J. Virol. (2000) 74(9):4404-4413.
136. CONNOR RI, SHERIDAN KE, CERADINI D et al.: Change in coreceptor use coreceptor use correlates with disease progression in HIV-1-infected individuals. J. Exp. Med. (1997) 185(4):621-628.
137. RUSCONI S, LA SETA-CATAMANCIO S, KURTAGIC S et al.: Aminooxypentane- RANTES, an inhibitor of R5 human immunodeficiency virus type 1, increases the interferon gamma to interleukin 10 ratio without impairing cellular proliferation. AIDS Res. Hum. Retroviruses (1999) 15(10):861-867.
138. GORDON CJ, MUESING MA, PROUDFOOT AE et al.: Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion. J. Virol. (1999) 73(1):684-694.
139. PROUDFOOT AE, POWER CA, HOOGEWERF AJ et al.: Extension of recombinant human RANTES by the retention of the initiating methionine produces a potent antagonist. J. Biol. Chem. (1996) 271(5):2599-2603.
140. YLISASTIGUI L, VIZZAVONA J, DRAKOPOULOU E et al.: Synthetic full-length and truncated RANTES inhibit HIV-1 infection of primary macrophages. AIDS (1998) 12(9):977-984.
141. ARENZANA-SEISDEDOS F, VIRELIZIER JL, ROUSSET D et al.: HIV blocked by chemokine antagonist. Nature (1996) 383(6599):400.
142. POLO S, NARDESE V, DE SANTIS C et al.: Enhancement of the HIV-1 inhibitory activity of RANTES by modification of the N-terminal region: dissociation from CCR5 activation. Eur. J. Immunol. (2000) 30(11):3190-3198.
143. STRUYF S, DE MEESTER I, SCHARPE S et al.: Natural truncation of RANTES abolishes signaling through the CC chemokine receptors CCR1 and CCR3, impairs its chemotactic potency and generates a CC chemokine inhibitor. Eur. J. Immunol. (1998) 28(4):1262-1271.
144. ORAVECZ T, PALL M, RODERIQUEZ G et al.: Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage. J. Exp. Med. (1997) 186(11):1865-1872.
145. OLSON WC, KETAS TJ, NAGASHIMA KA et al.: Potent, broad-spectrum inhibition of HIV-1 by the CCR5 antibody PRO 140. Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (2000) Abstract 550.
146. MENTEN P, STRUYF S, SCHUTYSER E et al.: The LD78beta isoform of MIP-1alpha is the most potent CCR5 agonist and HIV-1-inhibiting chemokine. J. Clin. Invest. (1999) 104(4):R1-5.
147. NIBBS RJ, YANG J, LANDAU NR et al.: LD78beta, a non-allelic variant of human MIP-1alpha (LD78alpha), has enhanced receptor interactions and potent HIV suppressive activity. J. Biol. Chem. (1999) 274(25):17478-17483.
148. XIN X, SHIODA T, KATO A et al.: Enhanced anti-HIV-1 activity of CC-chemokine LD78beta, a non-allelic variant of MIP-1alpha/LD78alpha. FEBS Lett. (1999) 457(2):219-222.
149. GONG W, HOWARD OM, TURPIN JA et al.: Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication. J. Biol. Chem. (1998) 273(8):4289-4292.
150. FRANCHIN G, ZYBARTH G, DAI WW et al.: Lipopolysaccharide inhibits HIV-1 infection of monocyte-derived macrophages through direct and sustained down-regulation of CC chemokine receptor 5. J. Immunol. (2000) 164(5):2592-2601.
151. ALFANO M, SCHMIDTMAYEROVA H, AMELLA CA et al.: The B-oligomer of pertussis toxin deactivates CC chemokine receptor 5 and blocks entry of M-tropic HIV-1 strains. J. Exp. Med. (1999) 190(5):597-605.
152. SHEN W, LI B, WETZEL MA et al.: Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes. Blood (2000) 96(8):2887-2894.
153. YANG OO, SWANBERG SL, LU Z et al.: Enhanced inhibition of human immunodeficiency virus type 1 by Met-stromal-derived factor 1beta correlates with down-modulation of CXCR4. J. Virol. (1999) 73(6):4582-4589.
154. DORANZ BJ, GROVIT-FERBAS K, SHARRON MP et al: A small-molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor. J. Exp. Med. (1997) 186 (8): 1395-1400.
155. LUO Z, ZHOU N, LUO J et al: The role of positively charged residues in CXCR4 recognition probed with synthetic peptides. Biochem. Biophys. Res. Commun. (1999) 263(3):691-695.
156. O'BRIEN WA, SUMNER-SMITH M, MAO SH et al.: Anti-human immunodeficiency virus type 1 activity of an oligocationic compound mediated via gp 120 V3 interactions. J. Virol (1996) 70(5):2825-2831.
157. SCHOLS D, STRUYF S, VAN DAMME J et al.: Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J. Exp. Med. (1997) 186 (8): 1383-1388.
158. VAN GELDER J, WITVROUW M, PANNECOUQUE C et al: Evaluation of the potential of ion pair formation to improve the oral absorption of two potent antiviral compounds, AMD3100 and PMPA. Int. J. Pharm. (1999) 186(2): 127-136.
159. BLANCO J, BARRETINA J, HENSON G et al: The CXCR4 antagonist AMD3100 efficiently inhibits cell-surface-expressed human immunodeficiency virus type 1 envelope-induced apoptosis. Antimicrob. Agents Chemother. (2000) 44(1):51-56.
160. MURAKAMI T, ZHANG TY, KOYANAGI Y et al: Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection. J. Virol (1999) 73(9):7489-7496.
161. MURAKAMI T, NAKAJIMA T, KOYANAGI Y et al: A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. J. Exp. Med. (1997) 186 (8): 1389-1393.
162. TAMAMURA H, IMAI M, ISHIHARA T et al: Pharmacophore identification of a chemokine receptor (CXCR4) antagonist, T22 ([Tyr(5,12),Lys7]-polyphemusin II),
163. ARAKAKI R, TAMAMURA H, PREMANATHAN M et al.: T134, a small-molecule CXCR4 inhibitor, has no cross-drug resistance with AMD3100, a CXCR4 antagonist with a different structure. J. Virol. (1999) 73(2):1719-1723.
164. TAMAMURA H, XU Y, HATTORI T et al.: A low-molecular-weight inhibitor against the chemokine receptor CXCR4: a strong anti-HIV peptide T140. Biochem. Biophys. Res. Commun. (1998) 253(3):877-882.
165. DAELEMANS D, SCHOLS D, WITVROUW M et al.: 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. (2000) 57(1):116-124.
166. TAKAMUNE N, MISUMI S, SHOJI S: Cyclic zinc-dithiocarbamate-S,S′- dioxide blocks CXCR4-mediated HIV-1 infection. Biochem. Biophys. Res. Commun. (2000) 272(2):351-356.
167. XIAO H, NEUVEUT C, TIFFANY HL et al.: Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1. Proc. Natl. Acad. Sci. USA (2000) 97(21):11466-11471.
168. GHEZZI S, NOONAN DM, ALUIGI MG et al.: Inhibition of CXCR4-dependent HIV-1 infection by extracellular HIV-1 Tat. Biochem. Biophys. Res. Commun. (2000) 270(3):992-996.
169. NIBBS RJ, SALCEDO TW, CAMPBELL JD et al.: C-C chemokine receptor 3 antagonism by the beta-chemokine macrophage inflammatory protein 4, a property strongly enhanced by an amino-terminal alanine-methionine swap. J. Immunol. (2000) 164(3):1488-1497.
170. STRUYF S, PROOST P, SOZZANI S et al.: Enhanced anti-HIV-1 activity and altered chemotactic potency of NH2-terminally processed macrophage-derived chemokine (MDC) imply an additional MDC receptor. J. Immunol. (1998) 161(6):2672-2675.
171. PAL R, GARZINO-DEMO A, MARKHAM PD et al.: Inhibition of HIV-1 infection by the beta-chemokine MDC. Science (1997) 278(5338):695-698.
172. HOWARD OM, OPPENHEIM JJ, HOLLINGSHEAD MG et al.: Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that interferes with chemokine receptor function: a candidate for chemotherapeutic and microbicidal application. J. Med. Chem. (1998) 41(13):2184-2193.
173. HOWARD OM, KORTE T, TARASOVA NI et al.: Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function. J. Leukoc. Biol. (1998) 64(1):6-13.
174. VASSILIADOU N, TUCKER L, ANDERSON DJ: Progesterone-induced inhibition of chemokine receptor expression on peripheral blood mononuclear cells correlates with reduced HIV-1 infectability in vitro. J. Immunol. (1999) 162(12):7510-7518.
175. DENG X, UEDA H, SU SB et al.: A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R. Blood (1999) 94(4):1165-1173.
176. BAILER RT, LEE B, MONTANER LJ: IL-13 and TNF-alpha inhibit dual-tropic HIV-1 in primary macrophages by reduction of surface expression of CD4, chemokine receptors CCR5, CXCR4 and post-entry 177. viral gene expression. Eur. J. Immunol. (2000) 30(5):1340-1349.
177. LAZZARINO DA, DIEGO M, MUSI E et al.: CXCR4 and CCR5 expression by H9 T-cells is downregulated by a peptide-nucleic acid immunomodulator. Immunol. Lett. (2000) 74(3):189-195.
178. DETHEUX M, STANDKER L, VAKILI J et al.: Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties [In Process Citation]. J. Exp. Med. (2000) 192(10):1501-1508.
179. ZHOU N, LUO Z, LUO J et al.: A novel peptide antagonist of CXCR4 derived from the N-terminus of viral chemokine vMIP-II. Biochemistry (Mosc). (2000) 39(13):3782-3787.
180. CAYABYAB M, HINUMA S, FARZAN M et al.: Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. J. Virol. (2000) 74(24):11972-11976.
181. TARASOVA NI, RICE WG, MICHEJDA CJ: Inhibition of G-protein-coupled receptor function by disruption of transmembrane domain interactions. J. Biol. Chem. (1999) 274(49):34911-34915.
182. BORING L, GOSLING J, CLEARY M et al.: Decreased lesion formation in CCR2-/-mice reveals a role for chemokines in the initiation of atherosclerosis. Nature (1998) 394(6696):894-897.
183. RUBBERT A, COMBADIERE C, OSTROWSKI M et al.: Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry. J. Immunol. (1998) 160(8):3933-3941.
184. SHI HZ, HUMBLES A, GERARD C et al.: Lymph node trafficking and antigen presentation by endobronchial eosinophils. J. Clin. Invest. (2000) 105(7):945-953.
185. MCKNIGHT A, DITTMAR MT, MONIZ-PERIERA J et al.: A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4. J. Virol. (1998) 72(5):4065-4071.
186. STINE JT, WOOD C, HILL M et al.: KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells. Blood (2000) 95(4):1151-1157.
187. OWEN SM, ELLENBERGER D, RAYFIELD M et al.: Genetically divergent strains of human immunodeficiency virus type 2 use multiple coreceptors for viral entry. J. Virol. (1998) 72(7):5425-5432.
188. CHVATCHKO Y, HOOGEWERF AJ, MEYER A et al.: A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J. Exp. Med. (2000) 191(10):1755-1764.
189. JINNO A, SHIMIZU N, SODA Y et al.: Identification of the chemokine receptor TER1/CCR8 expressed in brain-derived cells and T cells as a new coreceptor for HIV-1 infection. Biochem. Biophys. Res. Commun. (1998) 243(2):497-502.
190. HORUK R, HESSELGESSER J, ZHOU Y et al.: The CC chemokine I-309 inhibits CCR8-dependent infection by diverse HIV-1 strains. J. Biol. Chem. (1998) 273(1):386-391.
191. FAURE F, MEYER L, COSTAGLIOLA D et al.: Rapid Progression to AIDS in HIV+ Individuals with a structural variant of the chemokine receptor CX3CR1. Science (2000) 287(5461):2274-2277.
192. COMBADIERE C, SALZWEDEL K, SMITH ED et al.: Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1. J. Biol. Chem. (1998) 273(37):23799-23804.
193. MATLOUBIAN M, DAVID A, ENGEL S et al.: A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nature Immunol. (2000) 1(4):298-304.
194. FARZAN M, CHOE H, MARTIN K et al.: Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. J. Exp. Med. (1997) 186(3):405-411.
195. SHIMIZU N, SODA Y, KANBE K et al.: An orphan G protein-coupled receptor, GPR1, acts as a coreceptor to allow replication of human immunodeficiency virus types 1 and 2 in brain-derived cells. J. Virol. (1999) 73(6):5231-5239.
196. SAMSON M, LABBE O, MOLLEREAU C et al.: Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry (Mosc). (1996) 35:3362-3367.
197. OWMAN C, GARZINO-DEMO A, COCCHI F et al.: The leukotriene B4 receptor functions as a novel type o1 isolates into CD4-positive cells. Proc. Natl. Acad. Sci. USA (1998) 95(16):9530-9534.
198. PLESKOFF O, TREBOUTE C, BRELOT A et al.: Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry. Science (1997) 276(5320):1874-1878.