Combinations of the first and next generations of Human Immunodeficiency Virus (HIV) fusion inhibitors exhibit a highly potent synergistic effect against enfuvirtide-sensitive and -resistant HIV type 1 strains

Journal of Virology

Volumn 83, Issue 16, 2009, Pages 7862-7872

  Pan, Chungen ^a,b   Cai, Lifeng ^b   Lu, Hong ^b   Qi, Zhi ^b   Jiang, Shibo ^b,c  

^a PEKING UNIVERSITY   (China)

^b NEW YORK BLOOD CENTER   (United States)

^c SOUTHERN MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ENFUVIRTIDE; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; T 1144; T 1249; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL RESISTANCE; ARTICLE; CELL ADHESION; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG POTENTIATION; DRUG PROTEIN BINDING; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; MONOTHERAPY; PRIORITY JOURNAL; STRAIN DIFFERENCE; VIRUS CELL INTERACTION;

AMINO ACID SEQUENCE; CELL LINE; DRUG COMBINATIONS; DRUG RESISTANCE, VIRAL; DRUG SYNERGISM; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV INFECTIONS; HIV-1; HUMANS; MEMBRANE FUSION; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 67749147470     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.00168-09     Document Type: Article

References (62)

1. Bellamy-McIntyre, A. K., C. S. Lay, S. Baar, A. L. Maerz, G. H. Talbo, H. E. Drummer, and P. Poumbourios. 2007. Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. J. Biol. Chem. 282:23104-23116.
2. Champagne, K., A. Shishido, and M. J. Root. 2009. Interactions of HIV-1 inhibitory peptide T20 with the gp41 N-HR coiled coil. J. Biol. Chem. 284:3619-3627.
3. Chan, D. C., C. T. Chutkowski, and P. S. Kim. 1998. Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target. Proc. Natl. Acad. Sci. USA 95:15613-15617.
4. 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.
5. Chan, D. C., and P. S. Kim. 1998. HIV entry and its inhibition. Cell 93:681-684.
6. Chang, D. K., and C. S. Hsu. 2007. Biophysical evidence of two docking sites of the carboxyl heptad repeat region within the amino heptad repeat region of gp41 of human immunodeficiency virus type 1. Antivir. Res. 74:51-58.
7. Chinnadurai, R., D. Rajan, J. Munch, and F. Kirchhoff. 2007. Human immunodeficiency virus type 1 variants resistant to first- and second-version fusion inhibitors and cytopathic in ex vivo human lymphoid tissue. J. Virol. 81:6563-6572.
8. Chou, T. C., and P. Talalay. 1984. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22:27-55.
9. Chou, T. C. 2006. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol. Rev. 58:621-681.
10. Delmedico, M., B. Bray, N. Cammack, D. Davison, J. Dwyer, L. Frick, N. Tvermoes, S. Wring, H. Zhang, and M. Greenberg. 2006. Next generation HIV peptide fusion inhibitor candidates achieve potent, durable suppression of virus replication in vitro and improved pharmacokinetic properties, abstr. 48. Abstr. 13th Conf. Retrovir. Oppor. Infect., 5 to 8 February 2006. Foundation for Retrovirology and Human Health, Alexandria, VA.
11. Dwyer, J. J., K. L. Wilson, D. K. Davison, S. A. Freel, J. E. Seedorff, S. A. Wring, N. A. Tvermoes, T. J. Matthews, M. L. Greenberg, and M. K. Delmedico. 2007. Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus. Proc. Natl. Acad. Sci. USA 104:12772-12777.
12. Edelhoch, H. 1967. Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry 6:1948-1954.
13. Eggink, D., C. E. Baldwin, Y. Deng, J. P. M. Langedijk, M. Lu, R. W. Sanders, and B. Berkhout. 2008. Selection of T1249-resistant human immunodeficiency virus type 1 variants. J. Virol. 82:6678-6688.
14. Eron, J. J., R. M. Gulick, J. A. Bartlett, T. Merigan, R. Arduino, J. M. Kilby, B. Yangco, A. Diers, C. Drobnes, R. DeMasi, M. Greenberg, T. Melby, C. Raskino, P. Rusnak, Y. Zhang, R. Spence, and G. D. Miralles. 2004. Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV. J. Infect. Dis. 189:1075-1083.
15. Golding, H., M. Zaitseva, E. de Rosny, L. R. King, J. Manischewitz, I. Sidorov, M. K. Gorny, S. Zolla-Pazner, D. S. Dimitrov, and C. D. Weiss. 2002. Dissection of human immunodeficiency virus type 1 entry with neutralizing antibodies to gp41 fusion intermediates. J. Virol. 76:6780-6790.
16. Greenberg, M. L., and N. Cammack. 2004. Resistance to enfuvirtide, the first HIV fusion inhibitor. J. Antimicrob. Chemother. 54:333-340.
17. Gustchina, E., C. A. Bewley, and G. M. Clore. 2008. Sequestering of the prehairpin intermediate of gp41 by peptide N36Mut(e,g) potentiates the human immunodeficiency virus type 1 neutralizing activity of monoclonal antibodies directed against the N-terminal helical repeat of gp41. J. Virol. 82:10032-10041.
18. He, Y., J. Cheng, H. Lu, J. Li, J. Hu, Z. Qi, Z. Liu, S. Jiang, and Q. Dai. 2008. Potent HIV fusion inhibitors against enfuvirtide-resistant HIV-1 strains. Proc. Natl. Acad. Sci. USA 105:16332-16337.
19. He, Y., Y. Xiao, H. Song, Q. Liang, D. Ju, X. Chen, H. Lu, W. Jing, S. Jiang, and L. Zhang. 2008. Design and evaluation of sifuvirtide, a novel HIV-1 fusion inhibitor. J. Biol. Chem. 283:11126-11134.
20. Jiang, S., K. Lin, and M. Lu. 1998. A conformation-specific monoclonal antibody reacting with fusion-active gp41 from the HIV-1 envelope glycoprotein. J. Virol. 72:10213-10217.
21. Jiang, S., K. Lin, N. Strick, and A. R. Neurath. 1993. HIV-1 inhibition by a peptide. Nature 365:113.
22. Jiang, S., K. Lin, N. Strick, and A. R. Neurath. 1993. Inhibition of HIV-1 infection by a fusion domain binding peptide from HIV-1 envelope glycoprotein gp41. Biochem. Biophys. Res. Commun. 195:533-538.
23. Jiang, S., H. Lu, S. Liu, Q. Zhao, Y. He, and A. K. Debnath. 2004. N-substituted pyrrole derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere with the gp41 six-helix bundle formation and block virus fusion. Antimicrob. Agents Chemother. 48:4349-4359.
24. Kilby, J. M., and J. J. Eron. 2003. Novel therapies based on mechanisms of HIV-1 cell entry. N. Engl. J. Med. 348:2228-2238.
25. Kliger, Y., S. A. Gallo, S. G. Peisajovich, I. Munoz-Barroso, S. Avkin, R. Blumenthal, and Y. Shai. 2001. Mode of action of an antiviral peptide from HIV-1. Inhibition at a post-lipid mixing stage. J. Biol. Chem. 276:1391-1397.
26. Labrosse, B., L. Morand-Joubert, A. Goubard, S. Rochas, J. L. Labernardiere, J. Pacanowski, J. L. Meynard, A. J. Hance, F. Clavel, and F. Mammano. 2006. Role of the envelope genetic context in the development of enfuvirtide resistance in human immunodeficiency virus type 1-infected patients. J. Virol. 80:8807-8819.
27. Lalezari, J. P., N. C. Bellos, K. Sathasivam, G. J. Richmond, C. J. Cohen, R. A. Myers, Jr., D. H. Henry, C. Raskino, T. Melby, H. Murchison, Y. Zhang, R. Spence, M. L. Greenberg, R. A. Demasi, and G. D. Miralles. 2005. T-1249 retains potent antiretroviral activity in patients who had experienced virological failure while on an enfuvirtide-containing treatment regimen. J. Infect. Dis. 191:1155-1163.
28. Lawless, M. K., S. Barney, K. I. Guthrie, T. B. Bucy, Jr., S. R. Petteway, and G. Merutka. 1996. HIV-1 membrane fusion mechanism: structural studies of the interactions between biologically active peptides from gp41. Biochemistry 35:13697-13708.
29. Liu, S., W. Jing, B. Cheung, H. Lu, J. Sun, X. Yan, J. Niu, J. Farmar, S. Wu, and S. Jiang. 2007. HIV gp41 C-terminal heptad repeat contains multifunctional domains: relation to mechanisms of action of anti-HIV peptides. J. Biol. Chem. 282:9612-9620.
30. Liu, S., H. Lu, Y. Xu, S. Wu, and S. Jiang. 2005. Different from the HIV fusion inhibitor C34, the anti-HIV drug Fuzeon (T-20) inhibits HIV-1 entry by targeting multiple sites in gp41 and gp120. J. Biol. Chem. 280:11259-11273.
31. Liu, S., S. Wu, and S. Jiang. 2007. HIV entry inhibitors targeting gp41: from polypeptides to small-molecule compounds. Curr. Pharm. Design. 13:143-162.
32. Liu, S., Q. Zhao, and S. Jiang. 2003. Determination of the HIV-1 gp41 postfusion conformation modeled by synthetic peptides: applicable for identification of the HIV-1 fusion inhibitors. Peptide 24:1303-1313.
33. Lu, H., Q. Zhao, Z. Xu, and S. Jiang. 2003. Automatic quantitation of HIV-1 mediated cell-to-cell fusion with a digital image analysis system (DIAS): application for rapid screening of HIV-1 fusion inhibitors. J. Virol. Methods 107:155-161.
34. Lu, J., S. G. Deeks, R. Hoh, G. Beatty, B. A. Kuritzkes, J. N. Martin, and D. R. Kuritzkes. 2006. Rapid emergence of enfuvirtide resistance in HIV-1-infected patients: results of a clonal analysis. J. Acquir. Immune Defic. Syndr. 43:60-64.
35. Lu, M., S. C. Blacklow, and P. S. Kim. 1995. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nat. Struct. Biol. 2:1075-1082.
36. Matthews, T., M. Salgo, M. Greenberg, J. Chung, R. DeMasi, and D. Bolognesi. 2004. Enfuvirtide: the first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes. Nat. Rev. Drug Discov. 3:215-225.
37. Melby, T., R. DeMasi, N. Cammack, G. D. Miralles, and M. L. Greenberg. 2007. Evolution of genotypic and phenotypic resistance during chronic treatment with the fusion inhibitor T-1249. AIDS Res. Hum. Retrovir. 23:1366-1373.
38. Menzo, S., A. Castagna, A. Monachetti, H. Hasson, A. Danise, E. Carini, P. Bagnarelli, A. Lazzarin, and M. Clementi. 2004. Genotype and phenotype patterns of human immunodeficiency virus type 1 resistance to enfuvirtide during long-term treatment. Antimicrob. Agents Chemother. 48:3253-3259.
39. Mink, M., S. M. Mosier, S. Janumpalli, D. Davison, L. Jin, T. Melby, P. Sista, J. Erickson, D. Lambert, S. A. Stanfield-Oakley, M. Salgo, N. Cammack, T. Matthews, and M. L. Greenberg. 2005. Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J. Virol. 79:12447-12454.
40. Morton, T. A., D. G. Myszka, and I. M. Chaiken. 1995. Interpreting complex binding kinetics from optical biosensors: a comparison of analysis by linearization, the integrated rate equation, and numerical integration. Anal. Biochem. 227:176-185.
41. Munoz-Barroso, I., S. Durell, K. Sakaguchi, E. Appella, and R. Blumenthal. 1998. Dilation of the human immunodeficiency virus-1 envelope glycoprotein fusion pore revealed by the inhibitory action of a synthetic peptide from gp41. J. Cell Biol. 140:315-323.
42. Nagashima, K. A., D. A. Thompson, S. I. Rosenfield, P. J. Maddon, T. Dragic, and W. C. Olson. 2001. 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. 183:1121-1125.
43. Pan, C., H. Lu, Z. Qi, and S. Jiang. 2009. Synergistic efficacy of combination of enfuvirtide and sifuvirtide, the first- and next-generation HIV-fusion inhibitors. AIDS 23:639-641.
44. Peisajovich, S. G., S. A. Gallo, R. Blumenthal, and Y. Shai. 2003. C-terminal octylation rescues an inactive T20 mutant: implications for the mechanism of HIV/SIV-induced membrane fusion. J. Biol. Chem. 278:21012-21017.
45. Qi, Z., W. Shi, N. Xue, C. Pan, W. Jing, K. Liu, and S. Jiang. 2008. Rationally designed anti-HIV peptides containing multifunctional domains as molecule probes for studying the mechanisms of action of the first and second generation HIV fusion inhibitors. J. Biol. Chem. 283:30376-30384.
46. Ray, N., J. E. Harrison, L. A. Blackburn, J. N. Martin, S. G. Deeks, and R. W. Doms. 2007. Clinical resistance to enfuvirtide does not affect susceptibility of human immunodeficiency virus type 1 to other classes of entry inhibitors. J. Virol. 81:3240-3250.
47. Ray, N., L. A. Blackburn, and R. W. Doms. 2009. HR-2 mutations in human immunodeficiency virus type 1 gp41 restore fusion kinetics delayed by HR-1 mutations that cause clinical resistance to enfuvirtide. J. Virol. 83:2989-2995.
48. Reeves, J. D., F. H. Lee, J. L. Miamidian, C. B. Jabara, M. M. Juntilla, and R. W. Doms. 2005. Enfuvirtide resistance mutations: impact on human immunodeficiency virus envelope function, entry inhibitor sensitivity, and virus neutralization. J. Virol. 79:4991-4999.
49. Reeves, J. D., J. L. Miamidian, M. J. Biscone, F. H. Lee, N. Ahmad, T. C. Pierson, and R. W. Doms. 2004. Impact of mutations in the coreceptor binding site on human immunodeficiency virus type 1 fusion, infection, and entry inhibitor sensitivity. J. Virol. 78:5476-5485.
50. Rimsky, L. T., D. C. Shugars, and T. J. Matthews. 1998. Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J. Virol. 72:986-993.
51. Sista, P. R., T. Melby, D. Davison, L. Jin, S. Mosier, M. Mink, E. L. Nelson, R. DeMasi, N. Cammack, M. P. Salgo, T. J. Matthews, and M. L. Greenberg. 2004. Characterization of determinants of genotypic and phenotypic resistance to enfuvirtide in baseline and on-treatment HIV-1 isolates. AIDS 18:1787-1794.
52. Tan, K., J. Liu, J. Wang, S. Shen, and M. Liu. 1997. Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc. Natl. Acad. Sci. USA 94:12303-12308.
53. Tremblay, C. L., F. Giguel, C. Kollmann, Y. Guan, T. C. Chou, B. M. Baroudy, and M. S. Hirsch. 2002. Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5 antagonist, with other antiretroviral agents in vitro. Antimicrob. Agents Chemother. 46:1336-1339.
54. Tremblay, C. L., C. Kollmann, F. Giguel, T. C. Chou, and M. S. Hirsch. 2000. Strong in vitro synergy between the fusion inhibitor T-20 and the CXCR4 blocker AMD-3100. J. Acquir. Immune Defic. Syndr. 25:99-102.
55. Trivedi, V. D., S. F. Cheng, C. W. Wu, R. Karthikeyan, C. J. Chen, and D. K. Chang. 2003. The LLSGIV stretch of the N-terminal region of HIV-1 gp41 is critical for binding to a model peptide, T20. Protein Eng. 16:311-317.
56. Wei, X., J. M. Decker, H. Liu, Z. Zhang, R. B. Arani, J. M. Kilby, M. S. Saag, X. Wu, G. M. Shaw, and J. C. Kappes. 2002. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob. Agents Chemother. 46:1896-1905.
57. 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 387:426-428.
58. Wexler-Cohen, Y., and Y. Shai. 2007. Demonstrating the C-terminal boundary of the HIV 1 fusion conformation in a dynamic ongoing fusion process and implication for fusion inhibition. FASEB J. 21:3677-3684.
59. Wild, C., T. Greenwell, and T. Matthews. 1993. A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res. Hum. Retrovir. 9:1051-1053.
60. Wild, C., T. Greenwell, D. Shugars, L. Rimsky-Clarke, and T. Matthews. 1995. The inhibitory activity of an HIV type 1 peptide correlates with its ability to interact with a leucine zipper structure. AIDS Res. Hum. Retrovir. 11:323-325.
61. Wild, C. T., D. C. Shugars, T. K. Greenwell, C. B. McDanal, and T. J. Matthews. 1994. Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc. Natl. Acad. Sci. USA 91:9770-9774.
62. Xu, L., S. Hue, S. Taylor, D. Ratcliffe, J. A. Workman, S. Jackson, P. A. Cane, and D. Pillay. 2002. Minimal variation in T-20 binding domain of different HIV-1 subtypes from antiretroviral-naive and -experienced patients. AIDS 16:1684-1686.