Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal

Retrovirology

Volumn 6, Issue , 2009, Pages

  Levin, Aviad ^a   Armon Omer, Ayelet ^a,d   Rosenbluh, Joseph ^a   Melamed Book, Naomi ^a   Graessmann, Adolf ^b   Waigmann, Elisabeth ^c   Loyter, Abraham ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b FREIE UNIVERSITÄT BERLIN   (Germany)

^c Vienna Biocenter   (Austria)

^d Rebecca Sieff Government Hospital   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; COMPLEMENTARY DNA; INTEGRASE; KARYOPHERIN ALPHA; INTEGRASE INHIBITOR;

AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; CELL CULTURE; CELL CYCLE ARREST; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; ENZYME INHIBITION; FLUORESCENCE ANALYSIS; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY; IN VIVO STUDY; MAMMAL CELL; MICROINJECTION; NONHUMAN; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TEMPERATURE SENSITIVE MUTANT; VIRUS REPLICATION; YEAST CELL; ACTIVE TRANSPORT; ANIMAL; CELL NUCLEUS; CELL STRAIN COS1; CERCOPITHECUS; CHEMISTRY; DRUG EFFECT; HELA CELL; HOST PATHOGEN INTERACTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; METABOLISM; PHYSIOLOGY; VIROLOGY; VIRUS DNA CELL DNA INTERACTION;

HUMAN IMMUNODEFICIENCY VIRUS 1; MAMMALIA;

ACTIVE TRANSPORT, CELL NUCLEUS; ALPHA KARYOPHERINS; ANIMALS; CELL NUCLEUS; CERCOPITHECUS AETHIOPS; COS CELLS; HELA CELLS; HIV INFECTIONS; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HOST-PATHOGEN INTERACTIONS; HUMANS; METABOLIC NETWORKS AND PATHWAYS; NUCLEAR LOCALIZATION SIGNALS; VIRUS INTEGRATION; VIRUS REPLICATION;

EID: 73149108847     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-6-112     Document Type: Article

References (71)

1. Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol 2007, 8:195-208.
2. Gorlich D, Kutay U. Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol 1999, 15:607-660.
3. Feldherr C, Akin D, Littlewood T, Stewart M. The molecular mechanism of translocation through the nuclear pore complex is highly conserved. J Cell Sci 2002, 115:2997-3005.
4. Lewis P, Hensel M, Emerman M. Human immunodeficiency virus infection of cells arrested in the cell cycle. EMBO J 1992, 11:3053-3058. 556788, 1322294.
5. Katz RA, Greger JG, Boimel P, Skalka AM. Human immunodeficiency virus type 1 DNA nuclear import and integration are mitosis independent in cycling cells. J Virol 2003, 77:13412-13417. 296078, 14645598.
6. Miller MD, Farnet CM, Bushman FD. Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition. J Virol 1997, 71:5382-5390. 191777, 9188609.
7. Suzuki Y, Craigie R. The road to chromatin - nuclear entry of retroviruses. Nat Rev Microbiol 2007, 5:187-196.
8. Gallay P, Hope T, Chin D, Trono D. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci USA 1997, 94:9825-9830. 23276, 9275210.
9. Haffar OK, Popov S, Dubrovsky L, Agostini I, Tang H, Pushkarsky T, Nadler SG, Bukrinsky M. Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex. J Mol Biol 2000, 299:359-368.
10. Jenkins Y, McEntee M, Weis K, Greene WC. Characterization of HIV-1 vpr nuclear import: analysis of signals and pathways. J Cell Biol 1998, 143:875-885. 2132945, 9817747.
11. Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau P. HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 2000, 101:173-185.
12. Llano M, Vanegas M, Fregoso O, Saenz D, Chung S, Peretz M, Poeschla EM. LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes. J Virol 2004, 78:9524-9537. 506940, 15308744.
13. Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, Debyser Z, Engelborghs Y. LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem 2003, 278:33528-33539.
14. Yamashita M, Perez O, Hope TJ, Emerman M. Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells. PLoS Pathog 2007, 3:1502-1510. 2042020, 17967060.
15. Sherman MP, Greene WC. Slipping through the door: HIV entry into the nucleus. Microbes Infect 2002, 4:67-73.
16. Woodward CL, Wang Y, Dixon WJ, Htun H, Chow SA. Subcellular localization of feline immunodeficiency virus integrase and mapping of its karyophilic determinant. J Virol 2003, 77:4516-4527. 152119, 12663758.
17. Zheng R, Jenkins TM, Craigie R. Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity. Proc Natl Acad Sci USA 1996, 93:13659-13664. 19383, 8942990.
18. Kulkosky J, Jones KS, Katz RA, Mack JP, Skalka AM. Residues critical for retroviral integrative recombination in a region that is highly conserved among retroviral/retrotransposon integrases and bacterial insertion sequence transposases. Mol Cell Biol 1992, 12:2331-2338. 364405, 1314954.
19. Chiu TK, Davies DR. Structure and function of HIV-1 integrase. Curr Top Med Chem 2004, 4:965-977.
20. Esposito D, Craigie R. HIV integrase structure and function. Adv Virus Res 1999, 52:319-333.
21. Chen Z, Yan Y, Munshi S, Li Y, Zugay-Murphy J, Xu B, Witmer M, Felock P, Wolfe A, Sardana V, Emini EA, Hazuda D, Kuo LC. X-ray structure of simian immunodeficiency virus integrase containing the core and C-terminal domain (residues 50-293)--an initial glance of the viral DNA binding platform. J Mol Biol 2000, 296:521-533.
22. Pluymers W, Cherepanov P, Schols D, De Clercq E, Debyser Z. Nuclear localization of human immunodeficiency virus type 1 integrase expressed as a fusion protein with green fluorescent protein. Virology 1999, 258:327-332.
23. Armon-Omer A, Graessmann A, Loyter A. A synthetic peptide bearing the HIV-1 integrase 161-173 amino acid residues mediates active nuclear import and binding to importin alpha: characterization of a functional nuclear localization signal. J Mol Biol 2004, 336:1117-1128.
24. Depienne C, Mousnier A, Leh H, Le Rouzic E, Dormont D, Benichou S, Dargemont C. Characterization of the nuclear import pathway for HIV-1 integrase. J Biol Chem 2001, 276:18102-18107.
25. Hearps AC, Jans DA. HIV-1 integrase is capable of targeting DNA to the nucleus via an importin alpha/beta-dependent mechanism. Biochem J 2006, 398:475-484. 1559465, 16716146.
26. Ao Z, Huang G, Yao H, Xu Z, Labine M, Cochrane AW, Yao X. Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication. J Biol Chem 2007, 282:13456-13467.
27. Christ F, Thys W, De Rijck J, Gijsbers R, Albanese A, Arosio D, Emiliani S, Rain JC, Benarous R, Cereseto A, Debyser Z. Transportin-SR2 imports HIV into the nucleus. Curr Biol 2008, 18:1192-1202.
28. Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, Tempe D, Vandekerckhove L, Moisant F, Ben-Slama L, Witvrouw M, Christ F, Rain JC, Dargemont C, Debyser Z, Benarous R. Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. J Biol Chem 2005, 280:25517-25523.
29. Zielske SP, Stevenson M. Importin 7 may be dispensable for human immunodeficiency virus type 1 and simian immunodeficiency virus infection of primary macrophages. J Virol 2005, 79:11541-11546. 1193637, 16103209.
30. Zaitseva L, Cherepanov P, Leyens L, Wilson SJ, Rasaiyaah J, Fassati A. HIV-1 exploits importin 7 to maximize nuclear import of its DNA genome. Retrovirology 2009, 6:11. 2660290, 19193229.
31. Yano R, Oakes M, Yamaghishi M, Dodd JA, Nomura M. Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae. Mol Cell Biol 1992, 12:5640-5651. 360503, 1448093.
32. Kerppola TK. Visualization of molecular interactions by fluorescence complementation. Nat Rev Mol Cell Biol 2006, 7:449-456. 2512262, 16625152.
33. Bouyac-Bertoia M, Dvorin JD, Fouchier RA, Jenkins Y, Meyer BE, Wu LI, Emerman M, Malim MH. HIV-1 infection requires a functional integrase NLS. Mol Cell 2001, 7:1025-1035.
34. Pietersz GA, Li W, Apostolopoulos V. A 16-mer peptide (RQIKIWFQNRRMKWKK) from antennapedia preferentially targets the Class I pathway. Vaccine 2001, 19:1397-1405.
35. Conti E, Kuriyan J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure Fold Des 2000, 8:329-338.
36. Strahl T, Hama H, DeWald DB, Thorner J. Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus. J Cell Biol 2005, 171:967-979. 1382337, 16365163.
37. Kalpana GV, Goff SP. Genetic analysis of homomeric interactions of human immunodeficiency virus type 1 integrase using the yeast two-hybrid system. Proc Natl Acad Sci USA 1993, 90:10593-10597. 47823, 8248150.
38. Cherepanov P, Ambrosio AL, Rahman S, Ellenberger T, Engelman A. Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75. Proc Natl Acad Sci USA 2005, 102:17308-17313. 1297672, 16260736.
39. Truant R, Cullen BR. The arginine-rich domains present in human immunodeficiency virus type 1 Tat and Rev function as direct importin beta-dependent nuclear localization signals. Mol Cell Biol 1999, 19:1210-1217. 116050, 9891055.
40. Kimpton J, Emerman M. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene. J Virol 1992, 66:2232-2239. 289016, 1548759.
41. Hayouka Z, Rosenbluh J, Levin A, Loya S, Lebendiker M, Veprintsev D, Kotler M, Hizi A, Loyter A, Friedler A. Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium. Proc Natl Acad Sci USA 2007, 104:8316-8321. 1895947, 17488811.
42. Dvorin JD, Bell P, Maul GG, Yamashita M, Emerman M, Malim MH. Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. J Virol 2002, 76:12087-12096. 136890, 12414950.
43. Limon A, Devroe E, Lu R, Ghory HZ, Silver PA, Engelman A. Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. J Virol 2002, 76:10598-10607. 136649, 12368302.
44. Ao Z, Fowke KR, Cohen EA, Yao X. Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Retrovirology 2005, 2:62. 1277849, 16232319.
45. Silver P, Sadler I, Osborne MA. Yeast proteins that recognize nuclear localization sequences. J Cell Biol 1989, 109:983-989. 2115749, 2670959.
46. Wendler P, Lehmann A, Janek K, Baumgart S, Enenkel C. The bipartite nuclear localization sequence of Rpn2 is required for nuclear import of proteasomal base complexes via karyopherin alphabeta and proteasome functions. J Biol Chem 2004, 279:37751-37762.
47. Rosenbluh J, Hayouka Z, Loya S, Levin A, Armon-Omer A, Britan E, Hizi A, Kotler M, Friedler A, Loyter A. Interaction between HIV-1 Rev and Integrase Proteins: A BASIS FOR THE DEVELOPMENT OF ANTI-HIV PEPTIDES. J Biol Chem 2007, 282:15743-15753.
48. Cole KC, McLaughlin HW, Johnson DI. Use of bimolecular fluorescence complementation to study in vivo interactions between Cdc42p and Rdi1p of Saccharomyces cerevisiae. Eukaryot Cell 2007, 6:378-387. 1828923, 17220465.
49. Chen A, Weber IT, Harrison RW, Leis J. Identification of amino acids in HIV-1 and avian sarcoma virus integrase subsites required for specific recognition of the long terminal repeat Ends. J Biol Chem 2006, 281:4173-4182. 2656937, 16298997.
50. Xu Z, Zheng Y, Ao Z, Clement M, Mouland AJ, Kalpana GV, Belhumeur P, Cohen EA, Yao X. Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Retrovirology 2008, 5:102. 2615443, 19014595.
51. Derdeyn CA, Decker JM, Sfakianos JN, Wu X, O'Brien WA, Ratner L, Kappes JC, Shaw GM, Hunter E. Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. J Virol 2000, 74:8358-8367. 116346, 10954535.
52. Cullen BR. Use of eukaryotic expression technology in the functional analysis of cloned genes. Methods Enzymol 1987, 152:684-704.
53. Schiestl RH, Gietz RD. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr Genet 1989, 16:339-346.
54. Gietz D, St Jean A, Woods RA, Schiestl RH. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res 1992, 20:1425. 312198, 1561104.
55. Armon-Omer A, Levin A, Hayouka Z, Butz K, Hoppe-Seyler F, Loya S, Hizi A, Friedler A, Loyter A. Correlation between shiftide activity and HIV-1 integrase inhibition by a peptide selected from a combinatorial library. J Mol Biol 2008, 376:971-982.
56. Chen JC, Krucinski J, Miercke LJ, Finer-Moore JS, Tang AH, Leavitt AD, Stroud RM. Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proc Natl Acad Sci USA 2000, 97:8233-8238. 26930, 10890912.
57. Cormack BP, Bertram G, Egerton M, Gow NA, Falkow S, Brown AJ. Yeast-enhanced green fluorescent protein (yEGFP) a reporter of gene expression in Candida albicans. Microbiology 1997, 143(Pt 2):303-311.
58. Magliery TJ, Wilson CG, Pan W, Mishler D, Ghosh I, Hamilton AD, Regan L. Detecting protein-protein interactions with a green fluorescent protein fragment reassembly trap: scope and mechanism. J Am Chem Soc 2005, 127:146-157.
59. Christianson TW, Sikorski RS, Dante M, Shero JH, Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene 1992, 110:119-122.
60. Fineberg K, Fineberg T, Graessmann A, Luedtke NW, Tor Y, Lixin R, Jans DA, Loyter A. Inhibition of nuclear import mediated by the Rev-arginine rich motif by RNA molecules. Biochemistry 2003, 42:2625-2633.
61. Loeb JD, Schlenstedt G, Pellman D, Kornitzer D, Silver PA, Fink GR. The yeast nuclear import receptor is required for mitosis. Proc Natl Acad Sci USA 1995, 92:7647-7651. 41202, 7644471.
62. Hu CD, Chinenov Y, Kerppola TK. Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol Cell 2002, 9:789-798.
63. Rosenbluh J, Kapelnikov A, Shalev DE, Rusnati M, Bugatti A, Loyter A. Positively charged peptides can interact with each other, as revealed by solid phase binding assays. Anal Biochem 2006, 352:157-168.
64. Hariton-Gazal E, Feder R, Mor A, Graessmann A, Brack-Werner R, Jans D, Gilon C, Loyter A. Targeting of nonkaryophilic cell-permeable peptides into the nuclei of intact cells by covalently attached nuclear localization signals. Biochemistry 2002, 41:9208-9214.
65. Graessmann M, Graessmann A. Microinjection of tissue culture cells. Methods Enzymol 1983, 101:482-492.
66. Levin A, Kutznetova L, Kahana R, Rubinstein-Guini M, Stram Y. Highly effective inhibition of Akabane virus replication by siRNA genes. Virus Res 2006, 120:121-127.
67. Levin A, Hayouka Z, Helfer M, Brack-Werner R, Friedler A, Loyter A. Peptides derived from HIV-1 integrase that bind Rev stimulate viral genome integration. PLoS ONE 2009, 4:e4155. 2607543, 19127291.
68. Zhang J, Scadden DT, Crumpacker CS. Primitive hematopoietic cells resist HIV-1 infection via p21. J Clin Invest 2007, 117:473-481. 1783820, 17273559.
69. Levin A, Rosenbluh J, Hayouka Z, Friedler A, Loyter A. Integration of HIV-1 DNA is regulated by interplay between viral Rev and cellular LEDGF/p75 proteins. Mol Med 2009, 2765407, 19855849.
70. Casabianca A, Gori C, Orlandi C, Forbici F, Federico Perno C, Magnani M. Fast and sensitive quantitative detection of HIV DNA in whole blood leucocytes by SYBR green I real-time PCR assay. Mol Cell Probes 2007, 21:368-378.
71. Butler SL, Hansen MS, Bushman FD. A quantitative assay for HIV DNA integration in vivo. Nat Med 2001, 7:631-634.