Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity

Retrovirology

Volumn 9, Issue , 2012, Pages

  van Maarseveen, Noortje M ^a   Andersson, Dan ^b   Lepšík, Martin ^b   Fun, Axel ^a   Schipper, Pauline J ^a   de Jong, Dorien ^a   Boucher, Charles A B ^a,c   Nijhuis, Monique ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY   (Czech Republic)

^c ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Cleavage; Gag; HIV 1; NC p1; Protease; Replicative capacity; Resistance

Indexed keywords

GAG PROTEIN; GLUTAMIC ACID; HUMAN IMMUNODEFICIENCY VIRUS PROTEIN; MUTANT PROTEIN; PROTEIN HXB2; PROTEIN NC; PROTEIN P1; PROTEINASE INHIBITOR; THREONINE; UNCLASSIFIED DRUG; VALINE; GAG PROTEIN P1, HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; NCP7 PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; P16 PROTEASE, HUMAN IMMUNODEFICIENCY VIRUS 1;

ARTICLE; CODON; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY; MICROBIAL ACTIVITY; MOLECULAR EVOLUTION; NONHUMAN; PROTEIN ANALYSIS; PROTEIN CLEAVAGE; PROTEIN INTERACTION; PROTEIN PROCESSING; VIRUS REPLICATION; VIRUS RESISTANCE; AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; DRUG EFFECT; ENZYMOLOGY; GENETICS; METABOLISM; MISSENSE MUTATION; NUCLEOTIDE SEQUENCE; PHYSIOLOGY; PROTEIN DEGRADATION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

AMINO ACID SUBSTITUTION; DNA MUTATIONAL ANALYSIS; DRUG RESISTANCE, VIRAL; GAG GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; HIV PROTEASE; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; MUTANT PROTEINS; MUTATION, MISSENSE; PROTEOLYSIS; VIRUS REPLICATION;

EID: 84859043686     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-9-29     Document Type: Article

References (37)

1. Condra JH, Schleif WA, Blahy OM, Gabryelski LJ, Graham DJ, Quintero JC, Rhodes A, Robbins HL, Roth E, Shivaprakash M, et al. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 1995, 374:569-571. 10.1038/374569a0, 7700387.
2. Kaplan AH, Michael SF, Wehbie RS, Knigge MF, Paul DA, Everitt L, Kempf DJ, Norbeck DW, Erickson JW, Swanstrom R. Selection of multiple human immunodeficiency virus type 1 variants that encode viral proteases with decreased sensitivity to an inhibitor of the viral protease. Proc Natl Acad Sci USA 1994, 91:5597-5601. 10.1073/pnas.91.12.5597, 44043, 8202533.
3. Molla A, Korneyeva M, Gao Q, Vasavanonda S, Schipper PJ, Mo HM, Markowitz M, Chernyavskiy T, Niu P, Lyons N, et al. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med 1996, 2:760-766. 10.1038/nm0796-760, 8673921.
4. Swanstrom R, Erona J. Human immunodeficiency virus type-1 protease inhibitors: therapeutic successes and failures, suppression and resistance. Pharmacol Ther 2000, 86:145-170. 10.1016/S0163-7258(00)00037-1, 10799712.
5. Croteau G, Doyon L, Thibeault D, McKercher G, Pilote L, Lamarre D. Impaired fitness of HIV-1 variants with high-level resistance to protease inhibitors. J Virol 1997, 71:1089-1096. 191160, 8995629.
6. Gulnik S, Suvorov LI, Liu B, Yu B, Anderson B, Mitsuya H, Erickson JW. Kinetic characterization and cross-resistance patterns of HIV-1 protease mutants selected under drug pressure. Biochem 1995, 34:9282-9287.
7. Mahalingam B, Louis JM, Reed CC, Adomat JM, Krouse J, Wang YF, Harrison RW, Weber IT. Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. Eur J Biochem 1999, 263:238-245. 10.1046/j.1432-1327.1999.00514.x, 10429209.
8. Quinones-Mateu ME, Arts EJ. HIV-1 Fitness:Implications for drug resistance, disease progression an global epidemic evolution. HIV sequence compendium 2001 2001, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Kuiken C, Foley B, Hahn B, Marx PA, McCutchan F, Mellors J.
9. Borman AM, Paulos S, Clavel F. Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug. J Gen Virol 1996, 77:419-426. 10.1099/0022-1317-77-3-419, 8601776.
10. Doyon L, Croteau G, Thibeault D, Poulin F, Pilote L, Lamarre D. Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors. J Virol 1996, 70:3763-3769. 190252, 8648711.
11. Maguire MF, Guinea R, Griffin P, Macmanus S, Elston RC, Wolfram J, Richards N, Hanlon MH, Porter DJ, Wrin T, et al. Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. J Virol 2002, 76:7398-7406. 10.1128/JVI.76.15.7398-7406.2002, 136352, 12097552.
12. Mammano F, Petit C, Clavel F. Resistance-associated loss of viral fitness in human immunodeficiency virus type 1: phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients. J Virol 1998, 72:7632-7637. 110025, 9696866.
13. Mammano F, Trouplin V, Zennou V, Clavel F. Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: Virus fitness in the absence and in the presence of drug. J Virol 2000, 74:8524-8531. 10.1128/JVI.74.18.8524-8531.2000, 116364, 10954553.
14. Nijhuis M, Schuurman R, de Jong D, Erickson J, Gustchina E, Albert J, Schipper P, Gulnik S, Boucher CAB. Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. AIDS 1999, 13:2349-2359. 10.1097/00002030-199912030-00006, 10597776.
15. Zhang Y-M, Imamichi H, Imamichi T, Lane HC, Falloon J, Vasudevachari MB, Salzman NP. Drug Resistance during Indinavir Therapy Is Caused by Mutations in the Protease Gene and in Its Gag Substrate Cleavage Sites. J Virol 1997, 71:6662-6670. 191944, 9261388.
16. Kolli M, Lastere S, Schiffer CA. Co-evolution of nelfinavir-resistant HIV-1 protease and the p1-p6 substrate. Virol 2006, 347:405-409.
17. Kolli M, Stawiski E, Chappey C, Schiffer CA. Human immunodeficiency virus type 1 protease-correlated cleavage site mutations enhance inhibitor resistance. J Virol 2009, 83:11027-11042. 10.1128/JVI.00628-09, 2772784, 19706699.
18. Nijhuis M, van Maarseveen NM, Lastere S, Schipper P, Coakley E, Glass B, Rovenska M, de JD, Chappey C, Goedegebuure IW, et al. A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. PLoS Med 2007, 4:e36. 10.1371/journal.pmed.0040036, 1769415, 17227139.
19. De Meyer S, Azijn H, Fransen E, De Baere I, Van Ginderen M, Maes B, de Bethune MP. The pathway leading to TMC114 resistance is different for TMC114 compared with other protease inhibitors. Antivir Ther 2006, 11:S24.
20. Nijhuis M, van Maarseveen NM, Verheyen J, Boucher CAB. Novel mechanisms of HIV protease inhibitor resistance. Current Opinion in HIV and AIDS 2008, 3:627-632. 10.1097/COH.0b013e3283136cd9, 19373034.
21. Dam E, Quercia R, Glass B, Descamps D, Launay O, Duval X, Krausslich HG, Hance AJ, Clavel F. Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. PLoS Pathog 2009, 5:e1000345. 10.1371/journal.ppat.1000345, 2652074, 19300491.
22. Cote HC, Brumme ZL, Harrigan PR. Human immunodeficiency virus type 1 protease cleavage site mutations associated with protease inhibitor cross-resistance selected by indinavir, ritonavir, and/or saquinavir. J Virol 2001, 75:589-594. 10.1128/JVI.75.2.589-594.2001, 113954, 11134271.
23. Verheyen J, Knops E, Kupfer B, Hamouda O, Somogyi S, Schuldenzucker U, Hoffmann D, Kaiser R, Pfister H, Kucherer C. Prevalence of C-terminal gag cleavage site mutations in HIV from therapy-naive patients. J Infect 2009, 58:61-67. 10.1016/j.jinf.2008.11.009, 19110315.
24. Ghosn J, Delaugerre C, Flandre P, Galimand J, Cohen-Codar I, Raffi F, Delfraissy JF, Rouzioux C, Chaix ML. Polymorphism in Gag gene cleavage sites of HIV-1 non-B subtype and virological outcome of a first-line lopinavir/ritonavir single drug regimen. PLoS One 2011, 6:e24798. 10.1371/journal.pone.0024798, 3176769, 21949754.
25. Pettit SC, Moody MD, Wehbie RS, Kaplan AH, Nantermet PV, Klein CA, Swanstrom R. The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions. J Virol 1994, 68:8017-8027. 237265, 7966591.
26. Prabu-Jeyabalan M, Nalivaika EA, King NM, Schiffer CA. Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. J Virol 2004, 78:12446-12454. 10.1128/JVI.78.22.12446-12454.2004, 525094, 15507631.
27. Pettit SC, Henderson GJ, Schiffer CA, Swanstrom R. Replacement of the P1 amino acid of human immunodeficiency virus type 1 Gag processing sites can inhibit or enhance the rate of cleavage by the viral protease. J Virol 2002, 76:10226-10233. 10.1128/JVI.76.20.10226-10233.2002, 136535, 12239298.
28. van Maarseveen NM, de JD, Boucher CA, Nijhuis M. An increase in viral replicative capacity drives the evolution of protease inhibitor-resistant human immunodeficiency virus type 1 in the absence of drugs. J Acquir Immune Defic Syndr 2006, 42:162-168. 10.1097/01.qai.0000219787.65915.56, 16645546.
29. Prabu-Jeyabalan M, Nalivaika EA, Romano K, Schiffer CA. Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate. J Virol 2006, 80:3607-3616. 10.1128/JVI.80.7.3607-3616.2006, 1440387, 16537628.
30. Feher A, Weber IT, Bagossi P, Boross P, Mahalingam B, Louis JM, Copeland TD, Torshin IY, Harrison RW, Tozser J. Effect of sequence polymorphism and drug resistance on two HIV-1 Gag processing sites. Eur J Biochem 2002, 269:4114-4120. 10.1046/j.1432-1033.2002.03105.x, 12180988.
31. van Maarseveen NM, Huigen MCDG, de Jong D, Smits AM, Boucher CAB, Nijhuis M. A novel real-time PCR assay to determine relative replication capacity for HIV-1 protease variants and/or reverse transcriptase variants. J Virol Methods 2006, 133:185-194. 10.1016/j.jviromet.2005.11.008, 16368153.
32. Moore JP, McKeating JA, Weiss RA, Sattentau QJ. Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science 1990, 250:1139-1142. 10.1126/science.2251501, 2251501.
33. Boucher CAB, Keulen W, van Bommel T, Nijhuis M, de Jong D, de Jong MD, Schipper P, Back NKT. Human immunodeficiency virus type 1 drug susceptibility determination by using recombinant viruses generated from patient sera tested in a cell-killing assay. Antim Ag Chemoth 1996, 40:2404-2409.
34. Weber J, Mesters JR, Lepsik M, Prejdova J, Svec M, Sponarova J, Mlcochova P, Skalicka K, Strisovsky K, Uhlikova T, et al. Unusual binding mode of an HIV-1 protease inhibitor explains its potency against multi-drug-resistant virus strains. J Mol Biol 2002, 324:739-754. 10.1016/S0022-2836(02)01139-7, 12460574.
35. Konvalinka J, Litera J, Weber J, Vondrasek J, Hradilek M, Soucek M, Pichova I, Majer P, Strop P, Sedlacek J, et al. Configurations of diastereomeric hydroxyethylene isosteres strongly affect biological activities of a series of specific inhibitors of human-immunodeficiency-virus proteinase. Eur J Biochem 1997, 250:559-566. 10.1111/j.1432-1033.1997.0559a.x, 9428710.
36. Strisovsky K, Tessmer U, Langner J, Konvalinka J, Krausslich HG. Systematic mutational analysis of the active-site threonine of HIV-1 proteinase: rethinking the "fireman's grip" hypothesis. Protein Sci 2000, 9:1631-1641. 10.1110/ps.9.9.1631, 2144712, 11045610.
37. Massova I, Kollman PA. Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding. Perspect Drug Discovery Des 2000, 18:113-135.