Mechanism of HIV-1 resistance to short-peptide fusion inhibitors targeting the Gp41 pocket

Journal of Virology

Volumn 89, Issue 11, 2015, Pages 5801-5811

  Su, Yang ^a   Chong, Huihiui ^a   Qiu, Zonglin ^a   Xiong, Shengwen ^a   He, Yuxian ^a  

^a INSTITUTE OF PATHOGEN BIOLOGY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARAGINE; ENFUVIRTIDE; GLUTAMIC ACID; GLYCOPROTEIN GP 41; LYSINE; SIFUVIRTIDE; GP41 PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; PEPTIDE; PEPTIDE FRAGMENT; PROTEIN BINDING;

AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CROSS RESISTANCE; DRUG EFFECT; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROPHOBICITY; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; SEQUENCE ALIGNMENT; SIGNAL TRANSDUCTION; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION; VIRUS ENVELOPE; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; MISSENSE MUTATION; MUTATION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

AMINO ACID SUBSTITUTION; DRUG RESISTANCE, VIRAL; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV-1; MUTATION; MUTATION, MISSENSE; PEPTIDE FRAGMENTS; PEPTIDES; PROTEIN BINDING;

EID: 84929649253     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.00373-15     Document Type: Article

References (60)

1. Eckert DM, Kim PS. 2001. Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem 70:777-810. http://dx.doi.org/10.1146/annurev.biochem.70.1.777.
2. Colman PM, Lawrence MC. 2003. The structural biology of type I viral membrane fusion. Nat Rev Mol Cell Biol 4:309-319. http://dx.doi.org/10.1038/nrm1076.
3. Chan DC, Fass D, Berger JM, Kim PS. 1997. Core structure of gp41 from the HIV envelope glycoprotein. Cell 89:263-273. http://dx.doi.org/10.1016/S0092-8674(00)80205-6.
4. Tan K, Liu J, Wang J, Shen S, Lu M. 1997. Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc Natl Acad Sci U S A 94: 12303-12308. http://dx.doi.org/10.1073/pnas.94.23.12303.
5. Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. 1997. Atomic structure of the ectodomain from HIV-1 gp41. Nature 387:426-430. http://dx.doi.org/10.1038/387426a0.
6. Eggink D, Berkhout B, Sanders RW. 2010. Inhibition of HIV-1 by fusion inhibitors. Curr Pharm Des 16:3716-3728. http://dx.doi.org/10.2174/138161210794079218.
7. He Y. 2013. Synthesized peptide inhibitors of HIV-1 gp41-dependent membrane fusion. Curr Pharm Des 19:1800-1809. http://dx.doi.org/10.2174/1381612811319100004.
8. Baldwin CE, Sanders RW, Deng Y, Jurriaans S, Lange JM, Lu M, Berkhout B. 2004. Emergence of a drug-dependent human immunodeficiency virus type 1 variant during therapy with the T20 fusion inhibitor. J Virol 78:12428-12437. http://dx.doi.org/10.1128/JVI.78.22.12428-12437.2004.
9. Greenberg ML, Cammack N. 2004. Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 54:333-340. http://dx.doi.org/10.1093/jac/dkh330.
10. Nameki D, Kodama E, Ikeuchi M, Mabuchi N, Otaka A, Tamamura H, Ohno M, Fujii N, Matsuoka M. 2005. Mutations conferring resistance to human immunodeficiency virus type 1 fusion inhibitors are restricted by gp41 and Rev-responsive element functions. J Virol 79:764-770. http://dx.doi.org/10.1128/JVI.79.2.764-770.2005.
11. Xu L, Pozniak A, Wildfire A, Stanfield-Oakley SA, Mosier SM, Ratcliffe D, Workman J, Joall A, Myers R, Smit E, Cane PA, Greenberg ML, Pillay D. 2005. Emergence and evolution of enfuvirtide resistance following long-term therapy involves heptad repeat 2 mutations within gp41. Antimicrob Agents Chemother 49:1113-1119. http://dx.doi.org/10.1128/AAC.49.3.1113-1119.2005.
12. Cabrera C, Marfil S, Garcia E, Martinez-Picado J, Bonjoch A, Bofill M, Moreno S, Ribera E, Domingo P, Clotet B, Ruiz L. 2006. Genetic evolution of gp41 reveals a highly exclusive relationship between codons 36, 38 and 43 in gp41 under long-term enfuvirtide-containing salvage regimen. AIDS 20:2075-2080. http://dx.doi.org/10.1097/QAD.0b013e3280102377.
13. Ray N, Harrison JE, Blackburn LA, Martin JN, Deeks SG, Doms RW. 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. http://dx.doi.org/10.1128/JVI.02413-06.
14. Svicher V, Aquaro S, D'Arrigo R, Artese A, Dimonte S, Alcaro S, Santoro MM, Di Perri G, Caputo SL, Bellagamba R, Zaccarelli M, Visco-Comandini U, Antinori A, Narciso P, Ceccherini-Silberstein F, Perno CF. 2008. Specific enfuvirtide-associated mutational pathways in HIV-1 Gp41 are significantly correlated with an increase in CD4+ cell count, despite virological failure. J Infect Dis 197:1408-1418. http://dx.doi.org/10.1086/587693.
15. Shimura K, Nameki D, Kajiwara K, Watanabe K, Sakagami Y, Oishi S, Fujii N, Matsuoka M, Sarafianos SG, Kodama EN. 2010. Resistance profiles of novel electrostatically constrained HIV-1 fusion inhibitors. J Biol Chem 285:39471-39480. http://dx.doi.org/10.1074/jbc.M110.145789.
16. Eggink D, Bontjer I, Langedijk JP, Berkhout B, Sanders RW. 2011. Resistance of human immunodeficiency virus type 1 to a third-generation fusion inhibitor requires multiple mutations in gp41 and is accompanied by a dramatic loss of gp41 function. J Virol 85:10785-10797. http://dx.doi.org/10.1128/JVI.05331-11.
17. Liu Z, Shan M, Li L, Lu L, Meng S, Chen C, He Y, Jiang S, Zhang L. 2011. In vitro selection and characterization of HIV-1 variants with increased resistance to sifuvirtide, a novel HIV-1 fusion inhibitor. J Biol Chem 286:3277-3287. http://dx.doi.org/10.1074/jbc.M110.199323.
18. He Y, Xiao Y, Song H, Liang Q, Ju D, Chen X, Lu H, Jing W, Jiang S, Zhang L. 2008. Design and evaluation of sifuvirtide, a novel HIV-1 fusion inhibitor. J Biol Chem 283:11126-11134. http://dx.doi.org/10.1074/jbc.M800200200.
19. Dwyer JJ, Wilson KL, Davison DK, Freel SA, Seedorff JE, Wring SA, Tvermoes NA, Matthews TJ, Greenberg ML, Delmedico MK. 2007. Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus. Proc Natl Acad Sci U S A 104: 12772-12777. http://dx.doi.org/10.1073/pnas.0701478104.
20. Otaka A, Nakamura M, Nameki D, Kodama E, Uchiyama S, Nakamura S, Nakano H, Tamamura H, Kobayashi Y, Matsuoka M, Fujii N. 2002. Remodeling of gp41-C34 peptide leads to highly effective inhibitors of the fusion of HIV-1 with target cells. Angew Chem Int Ed Engl 41:2937-2940. http://dx.doi.org/10.1002/1521-3773(20020816)41:16<2937::AIDANIE2937>3.0.CO;2-J.
21. Eggink D, Baldwin CE, Deng Y, Langedijk JP, Lu M, Sanders RW, Berkhout B. 2008. Selection of T1249-resistant human immunodeficiency virus type 1 variants. J Virol 82:6678-6688. http://dx.doi.org/10.1128/JVI.00352-08.
22. Chan DC, Chutkowski CT, Kim PS. 1998. Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target. Proc Natl Acad Sci U S A 95:15613-15617. http://dx.doi.org/10.1073/pnas.95.26.15613.
23. Chan DC, Kim PS. 1998. HIV entry and its inhibition. Cell 93:681-684. http://dx.doi.org/10.1016/S0092-8674(00)81430-0.
24. Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS. 1999. Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket. Cell 99:103-115. http://dx.doi.org/10.1016/S0092-8674(00)80066-5.
25. Welch BD, VanDemark AP, Heroux A, Hill CP, Kay MS. 2007. Potent D-peptide inhibitors of HIV-1 entry. Proc Natl Acad Sci USA 104:16828-16833. http://dx.doi.org/10.1073/pnas.0708109104.
26. Steffen I, Pohlmann S. 2010. Peptide-based inhibitors of the HIV envelope protein and other class I viral fusion proteins. Curr Pharm Des 16: 1143-1158. http://dx.doi.org/10.2174/138161210790963751.
27. Welch BD, Francis JN, Redman JS, Paul S, Weinstock MT, Reeves JD, Lie YS, Whitby FG, Eckert DM, Hill CP, Root MJ, Kay MS. 2010. Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance. J Virol 84:11235-11244. http://dx.doi.org/10.1128/JVI.01339-10.
28. Yu F, Lu L, Liu Q, Yu X, Wang L, He E, Zou P, Du L, Sanders RW, Liu S, Jiang S. 2014. ADS-J1 inhibits HIV-1 infection and membrane fusion by targeting the highly conserved pocket in the gp41 NHR-trimer. Biochim Biophys Acta 1838:1296-1305. http://dx.doi.org/10.1016/j.bbamem.2013.12.022.
29. Jiang S, Lu H, Liu S, Zhao Q, He Y, Debnath AK. 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. http://dx.doi.org/10.1128/AAC.48.11.4349-4359.2004.
30. Chong H, Yao X, Qiu Z, Qin B, Han R, Waltersperger S, Wang M, Cui S, He Y. 2012. Discovery of critical residues for viral entry and inhibition through structural insight of HIV-1 fusion inhibitor CP621-652. J Biol Chem 287:20281-20289. http://dx.doi.org/10.1074/jbc.M112.354126.
31. Chong H, Yao X, Sun J, Qiu Z, Zhang M, Waltersperger S, Wang M, Cui S, He Y. 2012. The M-T hook structure is critical for design of HIV-1 fusion inhibitors. J Biol Chem 287:34558-34568. http://dx.doi.org/10.1074/jbc.M112.390393.
32. Chong H, Yao X, Qiu Z, Sun J, Zhang M, Waltersperger S, Wang M, Liu SL, Cui S, He Y. 2013. Short-peptide fusion inhibitors with high potency against wild-type and enfuvirtide-resistant HIV-1. FASEB J 27:1203-1213. http://dx.doi.org/10.1096/fj.12-222547.
33. Chong H, Qiu Z, Sun J, Qiao Y, Li X, He Y. 2014. Two M-T hook residues greatly improve the antiviral activity and resistance profile of the HIV-1 fusion inhibitor SC29EK. Retrovirology 11:40. http://dx.doi.org/10.1186/1742-4690-11-40.
34. Chong H, Yao X, Qiu Z, Sun J, Qiao Y, Zhang M, Wang M, Cui S, He Y. 2014. The M-T hook structure increases the potency of HIV-1 fusion inhibitor sifuvirtide and overcomes drug resistance. J Antimicrob Chemother 69:2759-2769. http://dx.doi.org/10.1093/jac/dku183.
35. Chong H, Qiu Z, Su Y, Yang L, He Y. 2015. Design of a highly potent HIV-1 fusion inhibitor targeting the gp41 pocket. AIDS 29:13-21. http://dx.doi.org/10.1097/QAD.0000000000000498.
36. Gill SC, von Hippel PH. 1989. Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem 182:319-326. http://dx.doi.org/10.1016/0003-2697(89)90602-7.
37. Chong H, Xu S, Zhang C, Nie J, Wang Y. 2009. Mutation L33M in the HR1 region of HIV-1 gp41 may play a role in T20 resistance. J Clin Virol 45:255-258. http://dx.doi.org/10.1016/j.jcv.2009.05.001.
38. Chong H, Yao X, Zhang C, Cai L, Cui S, Wang Y, He Y. 2012. Biophysical property and broad anti-HIV activity of albuvirtide, a 3-maleimimidopropionic acid-modified peptide fusion inhibitor. PLoS One 7:e32599. http://dx.doi.org/10.1371/journal.pone.0032599.
39. He Y, Liu S, Li J, Lu H, Qi Z, Liu Z, Debnath AK, Jiang S. 2008. Conserved salt bridge between the N-and C-terminal heptad repeat regions of the human immunodeficiency virus type 1 gp41 core structure is critical for virus entry and inhibition. J Virol 82:11129-11139. http://dx.doi.org/10.1128/JVI.01060-08.
40. Jiang S, Lin K, Lu M. 1998. A conformation-specific monoclonal antibody reacting with fusion-active gp41 from the human immunodeficiency virus type 1 envelope glycoprotein. J Virol 72:10213-10217.
41. Li J, Chen X, Huang J, Jiang S, Chen YH. 2009. Identification of critical antibody-binding sites in the HIV-1 gp41 six-helix bundle core as potential targets for HIV-1 fusion inhibitors. Immunobiology 214:51-60. http://dx.doi.org/10.1016/j.imbio.2008.04.005.
42. Lobritz MA, Ratcliff AN, Arts EJ. 2010. HIV-1 entry, inhibitors, and resistance. Viruses 2:1069-1105. http://dx.doi.org/10.3390/v2051069.
43. Ashkenazi A, Wexler-Cohen Y, Shai Y. 2011. Multifaceted action of Fuzeon as virus-cell membrane fusion inhibitor. Biochim Biophys Acta 1808:2352-2358. http://dx.doi.org/10.1016/j.bbamem.2011.06.020.
44. Naito T, Izumi K, Kodama E, Sakagami Y, Kajiwara K, Nishikawa H, Watanabe K, Sarafianos SG, Oishi S, Fujii N, Matsuoka M. 2009. SC29EK, a peptide fusion inhibitor with enhanced alpha-helicity, inhibits replication of human immunodeficiency virus type 1 mutants resistant to enfuvirtide. Antimicrob Agents Chemother 53:1013-1018. http://dx.doi.org/10.1128/AAC.01211-08.
45. Rimsky LT, Shugars DC, Matthews TJ. 1998. Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J Virol 72:986-993.
46. Lohrengel S, Hermann F, Hagmann I, Oberwinkler H, Scrivano L, Hoffmann C, von Laer D, Dittmar MT. 2005. Determinants of human immunodeficiency virus type 1 resistance to membrane-anchored gp41-derived peptides. J Virol 79:10237-10246. http://dx.doi.org/10.1128/JVI.79.16.10237-10246.2005.
47. Mink M, Mosier SM, Janumpalli S, Davison D, Jin L, Melby T, Sista P, Erickson J, Lambert D, Stanfield-Oakley SA, Salgo M, Cammack N, Matthews T, Greenberg ML. 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. http://dx.doi.org/10.1128/JVI.79.19.12447-12454.2005.
48. Wang W, De Feo CJ, Zhuang M, Vassell R, Weiss CD. 2011. Selection with a peptide fusion inhibitor corresponding to the first heptad repeat of HIV-1 gp41 identifies two genetic pathways conferring cross-resistance to peptide fusion inhibitors corresponding to the first and second heptad repeats (HR1 and HR2) of gp41. J Virol 85:12929-12938. http://dx.doi.org/10.1128/JVI.05391-11.
49. Zhuang M, Wang W, De Feo CJ, Vassell R, Weiss CD. 2012. Trimeric, coiled-coil extension on peptide fusion inhibitor of HIV-1 influences selection of resistance pathways. J Biol Chem 287:8297-8309. http://dx.doi.org/10.1074/jbc.M111.324483.
50. Eggink D, Langedijk JP, Bonvin AM, Deng Y, Lu M, Berkhout B, Sanders RW. 2009. Detailed mechanistic insights into HIV-1 sensitivity to three generations of fusion inhibitors. J Biol Chem 284:26941-26950. http://dx.doi.org/10.1074/jbc.M109.004416.
51. Yao X, Chong H, Zhang C, Waltersperger S, Wang M, Cui S, He Y. 2012. Broad antiviral activity and crystal structure of HIV-1 fusion inhibitor sifuvirtide. J Biol Chem 287:6788-6796. http://dx.doi.org/10.1074/jbc.M111.317883.
52. Ray N, Blackburn LA, Doms RW. 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. http://dx.doi.org/10.1128/JVI.02496-08.
53. De Feo CJ, Wang W, Hsieh ML, Zhuang M, Vassell R, Weiss CD. 2014. Resistance to N-peptide fusion inhibitors correlates with thermodynamic stability of the gp41 six-helix bundle but not HIV entry kinetics. Retrovirology 11:86. http://dx.doi.org/10.1186/s12977-014-0086-8.
54. Berkhout B, Sanders RW. 2011. Molecular strategies to design an escapeproof antiviral therapy. Antiviral Res 92:7-14. http://dx.doi.org/10.1016/j.antiviral.2011.04.002.
55. Loutfy MR, Raboud JM, Montaner JS, Antoniou T, Wynhoven B, Smaill F, Rouleau D, Gill J, Schlech W, Brumme ZL, Mo T, Gough K, Rachlis A, Harrigan PR, Walmsley SL. 2007. Assay of HIV gp41 amino acid sequence to identify baseline variation and mutation development in patients with virologic failure on enfuvirtide. Antiviral Res 75:58-63. http://dx.doi.org/10.1016/j.antiviral.2006.11.011.
56. Poveda E, Rodes B, Labernardiere JL, Benito JM, Toro C, Gonzalez-Lahoz J, Faudon JL, Clavel F, Schapiro J, Soriano V. 2004. Evolution of genotypic and phenotypic resistance to enfuvirtide in HIV-infected patients experiencing prolonged virologic failure. J Med Virol 74:21-28. http://dx.doi.org/10.1002/jmv.20141.
57. Sivaraman V, Zhang L, Meissner EG, Jeffrey JL, Su L. 2009. The heptad repeat 2 domain is a major determinant for enhanced human immunodeficiency virus type 1 (HIV-1) fusion and pathogenicity of a highly pathogenic HIV-1 Env. J Virol 83:11715-11725. http://dx.doi.org/10.1128/JVI.00649-09.
58. Izumi K, Kodama E, Shimura K, Sakagami Y, Watanabe K, Ito S, Watabe T, Terakawa Y, Nishikawa H, Sarafianos SG, Kitaura K, Oishi S, Fujii N, Matsuoka M. 2009. Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. J Biol Chem 284:4914-4920. http://dx.doi.org/10.1074/jbc.M807169200.
59. Desmezieres E, Gupta N, Vassell R, He Y, Peden K, Sirota L, Yang Z, Wingfield P, Weiss CD. 2005. Human immunodeficiency virus (HIV) gp41 escape mutants: cross-resistance to peptide inhibitors of HIV fusion and altered receptor activation of gp120. J Virol 79:4774-4781. http://dx.doi.org/10.1128/JVI.79.8.4774-4781.2005.
60. Wang LX, Song H, Liu S, Lu H, Jiang S, Ni J, Li H. 2005. Chemoenzymatic synthesis of HIV-1 gp41 glycopeptides: effects of glycosylation on the anti-HIV activity and alpha-helix bundle-forming ability of peptide C34. Chembiochem 6:1068-1074. http://dx.doi.org/10.1002/cbic.200400440.