Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase

Journal of Virology

Volumn 89, Issue 6, 2015, Pages 3163-3175

  Quashie, Peter K ^a,b   Oliviera, Maureen ^a   Veres, Tamar ^a   Osman, Nathan ^a,c   Han, Ying Shan ^a   Hassounah, Said ^a,b   Lie, Yolanda ^d   Huang, Wei ^d   Mesplède, Thibault ^a   Wainberg, Mark A ^a,b,c  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c MCGILL UNIVERSITY   (Canada)

^d MONOGRAM BIOSCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; DOLUTEGRAVIR; ELVITEGRAVIR; GLUTAMIC ACID; GLYCINE; HISTIDINE; INTEGRASE; LYSINE; RALTEGRAVIR; TYROSINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

AMINO ACID SUBSTITUTION; ARTICLE; CELL FREE SYSTEM; CONTROLLED STUDY; ENZYME ACTIVITY; GENOTYPE; HUMAN IMMUNODEFICIENCY VIRUS 1; INTEGRASE GENE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY; VIRUS REPLICATION; VIRUS RESISTANCE; AMINO ACID SEQUENCE; ANTIVIRAL RESISTANCE; CELL LINE; CHEMISTRY; CLASSIFICATION; DRUG EFFECTS; ENZYMOLOGY; GENETICS; HIV INFECTIONS; HUMAN; METABOLISM; MISSENSE MUTATION; MOLECULAR GENETICS; VIROLOGY;

HUMAN IMMUNODEFICIENCY VIRUS;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANTI-HIV AGENTS; CELL LINE; DRUG RESISTANCE, VIRAL; HIV INFECTIONS; HIV INTEGRASE; HIV-1; HUMANS; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; SEQUENCE ALIGNMENT;

EID: 84923206490     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.03353-14     Document Type: Article

References (47)

1. Kommer C. 2013. New UNAIDS figures. Kinderkrankenschwester 32:78. (In German.).
2. International Association of Physicians in AIDS Care. 2003. HAART slashed AIDS death rates by 80 percent. IAPAC Mon 9:279.
3. Stephenson J. 1999. The art of 'HAART': researchers probe the limits of aggressive HIV treatments. JAMA 277:614-616. http://dx.doi.org/10 .1001/jama.1997.03540320016008.
4. Williams A, Friedland G. 1997. Adherence, compliance, and HAART. AIDS Clin Care 9:51-54, 58.
5. Asahchop EL, Wainberg MA, Sloan RD, Tremblay CL. 2012. Antiviral drug resistance and the need for development of new HIV-1 reverse transcriptase inhibitors. Antimicrob Agents Chemother 56:5000-5008. http://dx.doi.org/10.1128/AAC.00591-12.
6. Sarafianos SG, Das K, Hughes SH, Arnold E. 2004. Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases. Curr Opin Struct Biol 14:716-730. http://dx.doi.org/10 .1016/j.sbi.2004.10.013.
7. Quashie PK, Sloan RD, Wainberg MA. 2012. Novel therapeutic strategies targeting HIV integrase. BMC Med 10:34. http://dx.doi.org/10.1186/1741-7015-10-34.
8. FDA. 2007. FDA approval of Isentress (raltegravir). Food and Drug Administration, Washington, DC.
9. Medical Letter on Drugs and Therapeutics. 2012. A 4-drug combination (Stribild) for HIV. Med Lett Drugs Ther 54:95-96.
10. Medical Letter on Drugs and Therapeutics. 2013. Dolutegravir (Tivicay) for HIV. Med Lett Drugs Ther 55:77-79.
11. Krishnan L, Li X, Naraharisetty HL, Hare S, Cherepanov P, Engelman A. 2010. Structure-based modeling of the functional HIV-1 intasome and its inhibition. Proc Natl Acad Sci U S A 107:15910-15915. http://dx.doi .org/10.1073/pnas.1002346107.
12. Blanco JL, Varghese V, Rhee SY, Gatell JM, Shafer RW. 2011. HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis 203:1204-1214. http://dx.doi.org/10.1093/infdis/jir025.
13. Mesplede T, Quashie PK, Zanichelli V, Wainberg MA. 2014. Integrase strand transfer inhibitors in the management of HIV-positive individuals. Ann Med 46:123-129. http://dx.doi.org/10.3109/07853890.2014.883169.
14. Wainberg MA, Mesplede T, Quashie PK. 2012. The development of novel HIV integrase inhibitors and the problem of drug resistance. Curr Opin Virol 2:656-662. http://dx.doi.org/10.1016/j.coviro.2012.08.007.
15. Mesplede T, Quashie PK, Wainberg MA. 2012. Resistance to HIV integrase inhibitors. Curr Opin HIV AIDS 7:401-408. http://dx.doi.org/10 .1097/COH.0b013e328356db89.
16. Quashie PK, Mesplede T, Han YS, Oliveira M, Singhroy DN, Fujiwara T, Underwood MR, Wainberg MA. 2012. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J Virol 86:2696-2705. http://dx.doi.org/10.1128/JVI.06591-11.
17. Mesplede T, Quashie PK, Osman N, Han Y, Singhroy DN, Lie Y, Petropoulos CJ, Huang W, Wainberg MA. 2013. Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology 10: 22. http://dx.doi.org/10.1186/1742-4690-10-22.
18. Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S. 2013. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 382:700-708. http://dx.doi.org/10.1016/S0140-6736(13)61221-0.
19. Quashie PK, Mesplede T, Han YS, Veres T, Osman N, Hassounah S, Sloan R, Xu HT, Wainberg MA. 2013. Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Antimicrob Agents Chemother 57:6223-6235. http://dx.doi.org/10 .1128/AAC.01835-13.
20. Bar-Magen T, Sloan RD, Donahue DA, Kuhl BD, Zabeida A, Xu H, Oliveira M, Hazuda DJ, Wainberg MA. 2010. Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. J Virol 84:9210-9216. http://dx.doi.org/10 .1128/JVI.01164-10.
21. Grobler JA, McKenna PM, Ly S, Stillmock K, Bahnck C, Danovich RM, Dornadula G, Hazuda DJ, Miller MD. 2009. Functionally irreversible inhibition of integration by slowly dissociating strand transfer inhibitors, abstr O-10. Abstr 10th Int Workshop Clin Pharmacol HIV Ther, Amsterdam, Netherlands.
22. Bar-Magen T, Sloan RD, Faltenbacher VH, Donahue DA, Kuhl BD, Oliveira M, Xu H, Wainberg MA. 2009. Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes. Retrovirology 6:103. http://dx.doi.org/10.1186/1742-4690-6-103.
23. Han YS, Quashie P, Mesplede T, Xu H, Mekhssian K, Fenwick C, Wainberg MA. 2012. A high-throughput assay for HIV-1 integrase 3'-processing activity using time-resolved fluorescence. J Virol Methods 184: 34-40. http://dx.doi.org/10.1016/j.jviromet.2012.05.003.
24. Dicker IB, Terry B, Lin Z, Li Z, Bollini S, Samanta HK, Gali V, Walker MA, Krystal MR. 2008. Biochemical analysis of HIV-1 integrase variants resistant to strand transfer inhibitors. J Biol Chem 283:23599-23609. http://dx.doi.org/10.1074/jbc.M804213200.
25. Tramontano E, Colla PL, Cheng YC. 1998. Biochemical characterization of the HIV-1 integrase 3-processing activity and its inhibition by phosphorothioate oligonucleotides. Biochemistry 37:7237-7243. http://dx.doi .org/10.1021/bi972792o.
26. Smolov M, Gottikh M, Tashlitskii V, Korolev S, Demidyuk I, Brochon JC, Mouscadet JF, Deprez E. 2006. Kinetic study of the HIV-1 DNA 3'-end processing. FEBS J 273:1137-1151. http://dx.doi.org/10.1111/j .1742-4658.2006.05139.x.
27. Eswar N, Eramian D, Webb B, Shen MY, Sali A. 2008. Protein structure modeling with MODELLER. Methods Mol Biol 426:145-159. http://dx .doi.org/10.1007/978-1-60327-058-8_8.
28. Zhang Y. 2009. I-TASSER: fully automated protein structure prediction in CASP8. Proteins 77(Suppl 9):100-113. http://dx.doi.org/10.1002/prot .22588.
29. Hare S, Maertens GN, Cherepanov P. 2012. 3'-processing and strand transfer catalysed by retroviral integrase in crystallo. EMBO J 31:3020-3028. http://dx.doi.org/10.1038/emboj.2012.118.
30. Buenavista MT, Roche DB, McGuffin LJ. 2012. Improvement of 3D protein models using multiple templates guided by single-template model quality assessment. Bioinformatics 28:1851-1857. http://dx.doi.org/10 .1093/bioinformatics/bts292.
31. Wang Q, Canutescu AA, Dunbrack RL, Jr. 2008. SCWRL and MolIDE: computer programs for side-chain conformation prediction and homology modeling. Nat Protoc 3:1832-1847. http://dx.doi.org/10.1038/nprot .2008.184.
32. Prlic A, Bliven S, Rose PW, Bluhm WF, Bizon C, Godzik A, Bourne PE. 2010. Pre-calculated protein structure alignments at the RCSB PDB website. Bioinformatics 26:2983-2985. http://dx.doi.org/10.1093/bioinformatics/btq572.
33. Sheik SS, Sundararajan P, Hussain AS, Sekar K. 2002. Ramachandran plot on the Web. Bioinformatics 18:1548-1549. http://dx.doi.org/10.1093/bioinformatics/18.11.1548.
34. Kolaskar AS, Sawant S. 1996. Prediction of conformational states of amino acids using a Ramachandran plot. Int J Pept Protein Res 47:110-116.
35. Malet I, Fourati S, Charpentier C, Morand-Joubert L, Armenia D, Wirden M, Sayon S, Van Houtte M, Ceccherini-Silberstein F, Brun-Vézinet F, Perno CF, Descamps D, Capt A, Calvez V, Marcelin AG. 2011. The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype. J Antimicrob Chemother 66:2827-2830. http://dx.doi.org/10.1093/jac/dkr389.
36. Thompson JD, Higgins DG, Gibson TJ. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673-4680. http://dx.doi.org/10.1093/nar/22.22.4673.
37. Wares M, Mesplede T, Quashie PK, Osman N, Han Y, Wainberg MA. 2014. The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Retrovirology 11:7. http://dx.doi.org/10.1186/1742-4690-11-7.
38. Collins DW, Jukes TH. 1994. Rates of transition and transversion in coding sequences since the human-rodent divergence. Genomics 20:386-396. http://dx.doi.org/10.1006/geno.1994.1192.
39. Engelman A, Liu Y, Chen H, Farzan M, Dyda F. 1997. Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase. J Virol 71:3507-3514.
40. Hare S, Smith SJ, Métifiot M, Jaxa-Chamiec A, Pommier Y, Hughes SH, Cherepanov P. 2011. Structural and functional analyses of the secondgeneration integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol 80:565-572. http://dx.doi.org/10.1124/mol.111.073189.
41. Mesplede T, Osman N, Wares M, Quashie PK, Hassounah S, Anstett K, Han Y, Singhroy DN, Wainberg MA. 2014. Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of theHIVintegrase enzyme and viral replication capacity. J Antimicrob Chemother 69:2733-2740. http://dx.doi.org/10.1093/jac/dku199.
42. Hardy I, Brenner B, Quashie P, Thomas R, Petropoulos C, Huang W, Moisi D, Wainberg MA, Roger M. Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. J Antimicrob Chemother, in press.
43. DeAnda F, Hightower KE, Nolte RT, Hattori K, Yoshinaga T, Kawasuji T, Underwood MR. 2013. Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. PLoS One 8:e77448. http://dx.doi.org/10.1371/journal.pone.0077448.
44. Bar-Magen T, Donahue DA, McDonough EI, Kuhl BD, Faltenbacher VH, Xu H, Michaud V, Sloan RD, Wainberg MA. 2010. HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays. AIDS 24:2171-2179. http://dx .doi.org/10.1097/QAD.0b013e32833cf265.
45. Hare S, Vos AM, Clayton RF, Thuring JW, Cummings MD, Cherepanov P. 2010. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc Natl Acad Sci U S A 107:20057-20062. http://dx.doi.org/10.1073/pnas.1010246107.
46. Oliveira M, Mesplede T, Quashie PK, Moisi D, Wainberg MA. 2014. Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. AIDS 28: 813-819. http://dx.doi.org/10.1097/QAD.0000000000000199.
47. Hassounah SA, Mesplede T, Quashie PK, Oliveira M, Sandstrom PA, Wainberg MA. 2014. Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. J Virol 88:9683-9692. http://dx.doi.org/10.1128/JVI.00947-14.