Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV

PLoS Pathogens

Volumn 3, Issue 3, 2007, Pages

  Hombrouck, Anneleen ^a   De Rijck, Jan ^a   Hendrix, Jelle ^b   Vandekerckhove, Linos ^a   Voet, Arnout ^b   De Maeyer, Marc ^b   Witvrouw, Myriam ^a   Engelborghs, Yves ^b   Christ, Frauke ^a   Gijsbers, Rik ^a   Debyser, Zeger ^a  

^a DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; INTEGRASE; LENS EPITHELIUM DERIVED GROWTH FACTOR; PROTEIN P75; VIRUS ENZYME; DNA; DNA BINDING PROTEIN; ENHANCED GREEN FLUORESCENT PROTEIN; GREEN FLUORESCENT PROTEIN; LENS EPITHELIUM-DERIVED GROWTH FACTOR; PEPTIDE FRAGMENT; SIGNAL PEPTIDE; UNCLASSIFIED DRUG; VIRUS DNA;

ARTICLE; CHROMOSOME ANALYSIS; ENZYME ACTIVITY; EVOLUTION; GENE MUTATION; HUMAN IMMUNODEFICIENCY VIRUS; KINETICS; LENTIVIRINAE; MUTAGENESIS; NONHUMAN; PROTEIN EXPRESSION; RETROVIRUS; T LYMPHOCYTE; VIRUS GENE; VIRUS REPLICATION; VIRUS RESISTANCE; X RAY CRYSTALLOGRAPHY; CELL LINE; CHROMOSOME; GENE EXPRESSION REGULATION; GENETICS; HELA CELL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; LEUKEMIA CELL LINE; METABOLISM; MUTATION; PHYSIOLOGY; VIRUS DNA CELL DNA INTERACTION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

CELL LINE; CHROMOSOMES; DNA; DNA, VIRAL; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION; GREEN FLUORESCENT PROTEINS; HELA CELLS; HIV INTEGRASE; HIV-1; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; JURKAT CELLS; MUTATION; PEPTIDE FRAGMENTS; VIRUS INTEGRATION; VIRUS REPLICATION;

EID: 34047200871     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.0030047     Document Type: Article

References (49)

1. Van Maele B, Busschots K, Vandekerckhove L, Christ F, Debyser Z (2006) Cellular co-factors of HIV-1 integration. Trends Biochem Sci 31: 98-105.
2. Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, et al. (2003) HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J Biol Chem 278: 372-381.
3. Turlure F, Devroe E, Silver PA, Engelman A (2004) Human cell proteins and human immunodeficiency virus DNA integration. Front Biosci 9: 3187-3208.
4. Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, et al. (2005) Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. J Biol Chem 280: 25517-25523.
5. Busschots K, Vercammen J, Emiliani S, Benarous R, Engelborghs Y, et al. (2005) The interaction of LEDGF/p75 with integrase is lentivirus-specific and promotes DNA binding. J Biol Chem 280: 17841-17847.
6. Llano M, Vanegas M, Fregoso O, Saenz D, Chung S, et al. (2004) 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 78: 9524-9537.
7. Cherepanov P (2007) LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res 35: 113-124.
8. Ge YZ, Pu MT, Gowher H, Wu HP, Ding JP, et al. (2004) Chromatin targeting of de novo DNA methyltransferases by the PWWP domain. J Biol Chem 279: 25447-25454.
9. Llano M, Vanegas M, Hutchins N, Thompson D, Delgado S, et al. (2006) Identification and characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. J Mol Biol 360: 760-773.
10. Cherepanov P, Devroe E, Silver PA, Engelman A (2004) Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase. J Biol Chem 279: 48883-48892.
11. Vanegas M, Llano M, Delgado S, Thompson D, Peretz M, et al. (2005) Identification of the LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin tethering. J Cell Sci 118: 1733-1743.
12. Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, et al. (2003) LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem 278: 33528-33539.
13. Llano M, Vanegas M, Fregoso O, Saenz D, Chung S, et al. (2004) 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 78: 9524-9537.
14. Ciuffi A, Llano M, Poeschla E, Hoffmann C, Leipzig J, et al. (2005) A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med 11: 1287-1289.
15. Vandegraaff N, Devroe E, Turlure F, Silver PA, Engelman A (2006) Biochemical and genetic analyses of integrase-interacting proteins lens epithelium-derived growth factor (LEDGF)/p75 and hepatoma-derived growth factor related protein 2 (HRP2) in preintegration complex function and HIV-1 replication. Virology 346: 415-426.
16. Vandekerckhove L, Christ F, Van Maele B, De Rijck J, Gijsbers R, et al. (2006) Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. J Virol 80: 1886-1896.
17. Llano M, Saenz DT, Meehan A, Wongthida P, Peretz M, et al. (2006) An essential role for LEDGF/p75 in HIV integration. Science 314: 461-464.
18. Zielske SP, Stevenson M (2006) Modest but reproducible inhibition of human immunodeficiency virus type 1 infection in macrophages following LEDGFp75 silencing. J Virol 80: 7275-7280.
19. De Rijck J, Vandekerckhove L, Gijsbers R, Hombrouck A, Hendrix J, et al. (2006) Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replication. J Virol 80: 11498-11509.
20. Cherepanov P, Sun ZY, Rahman S, Maertens G, Wagner G, et al. (2005) Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75. Nat Struct Mol Biol 12: 526-532.
21. Depienne C, Roques P, Creminon C, Fritsch L, Casseron R, et al. (2000) Cellular distribution and karyophilic properties of matrix, integrase, and Vpr proteins from the human and simian immunodeficiency viruses. Exp Cell Res 260: 387-395.
22. Pluymers W, Cherepanov P, Schols D, De Clercq E, Debyser Z (1999) Nuclear localization of human immunodeficiency virus type 1 integrase expressed as a fusion protein with green fluorescent protein. Virology 258: 327-332.
23. Cherepanov P, Pluymers W, Claeys A, Proost P, De Clercq E, et al. (2000) High-level expression of active HIV-1 integrase from a synthetic gene in human cells. FASEB J 14: 1389-1399.
24. Petit C, Schwartz O, Mammano F (1999) Oligomerization within virions and subcellular localization of human immunodeficiency virus type 1 integrase. J Virol 73: 5079-5088.
25. Limon A, Devroe E, Lu R, Ghory HZ, Silver PA, et al. (2002) 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 76: 10598-10607.
26. Devroe E, Engelman A, Silver PA (2003) Intracellular transport of human immunodeficiency virus type 1 integrase. J Cell Sci 116: 4401-4408.
27. Maertens G, Cherepanov P, Debyser Z, Engelborghs Y, Engelman A (2004) Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. J Biol Chem 279: 33421-33429.
28. Cherepanov P, Ambrosio AL, Rahman S, Ellenberger T, Engelman A (2005) Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75. Proc Natl Acad Sci U S A 102: 17308-17313.
29. Rahman S, Lu R, Vandegraaff N, Cherepanov P, Engelman A (2006) Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a strict correlation between in vitro protein binding and HIV-1 fitness. Virology 357: 79-90.
30. Fikkert V, Van Maele B, Vercammen J, Hantson A, Van Remoortel B, et al. (2003) Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. J Virol 77: 11459-11470.
31. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, et al. (2000) Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 287: 646-650.
32. Kuiken CL, Foley B, Hahn B, Korber B, McCutchan F, et al. (1999) Human retroviruses and AIDS 1999: A compilation and analysis of nucleic acid and amino acid sequences. Los Alamos (New Mexico): Theoretical Biology and Biophysics Group, Los Alamos National Laboratory.
33. Braaten D, Aberham C, Franke EK, Yin L, Phares W, et al. (1996) Cyclosporine A-resistant human immunodeficiency virus type 1 mutants demonstrate that Gag encodes the functional target of cyclophilin A. J Virol 70: 5170-5176.
34. Hatziioannou T, Perez-Caballero D, Cowan S, Bieniasz PD (2005) Cyclophilin interactions with incoming human immunodeficiency virus type 1 capsids with opposing effects on infectivity in human cells. J Virol 79: 176-183.
35. Carrington M, Dean M, Martin MP, O'Brien SJ (1999) Genetics of HIV-1 infection: Chemokine receptor CCR5 polymorphism and its consequences. Hum Mol Genet 8: 1939-1945.
36. Lutzke RA, Plasterk RH (1998) Structure-based mutational analysis of the C-terminal DNA-binding domain of human immunodeficiency virus type 1 integrase: Critical residues for protein oligomerization and DNA binding. J Virol 72: 4841-4848.
37. Kirsch RD, Joly E (1998) An improved PCR-mutagenesis strategy for twosite mutagenesis or sequence swapping between related genes. Nucl Acids Res 26: 1848-1850.
38. Geraerts M, Michiels M, Baekelandt V, Debyser Z, Gijsbers R (2005) Upscaling of lentiviral vector production by tangential flow filtration. J Gene Med 7: 1299-1310.
39. Miyoshi L, Taguchi H, Kobonishi I, Yoshimoto S, Ohtsuki Y, et al. (1982) Type C virus-producing cell lines derived from adult T cell leukemia. Gann Monogr 28: 219-228.
40. Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, et al. (1986) Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 59: 284-291.
41. Hubert J (1984) Spearman-Karber method. Bioassay. 2nd edition. Dubuque (Iowa): Hunt Publishing. pp. 65-66.
42. Van Maele B, De Rijck J, De Clercq E, Debyser Z (2003) Impact of the central polypurine tract on the kinetics of human immunodeficiency virus type 1 vector transduction. J Virol 77: 4685-4694.
43. Butler SL, Hansen MS, Bushman FD (2001) A quantitative assay for HIV DNA integration in vivo. Nat Med 7: 631-634.
44. Bushman FD, Craigie R (1991) Activities of human immunodeficiency virus (HIV) integration protein in vitro: Specific cleavage and integration of HIV DNA. Proc Natl Acad Sci U S A 88: 1339-1343.
45. Cherepanov P, Este JA, Rando RF, Ojwang JO, Reekmans G, et al. (1997) Mode of interaction of G-quartets with the integrase of human immunodeficiency virus type 1. Mol Pharmacol 52: 771-780.
46. Debyser Z, Cherepanov P, Pluymers W, De Clercq E (2001) Assays for the evaluation of HIV-1 integrase inhibitors. In: Schein CH, editor. Methods in molecular biology. Totowa (New Jersey): Humana Press. pp. 139-155.
47. Goldgur Y, Dyda F, Hickman AB, Jenkins TM, Craigie R, et al. (1998) Three new structures of the core domain of HIV-1 integrase: An active site that binds magnesium. Proc Natl Acad Sci U S A 95: 9150-9154.
48. Brooks B, Bruccoleri R, Olafson B, States D, Swaminathan S, et al. (1983) CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J Comp Chem 4: 87-217.
49. Delhaise P, Bardiaux M, De Maeyer M, Prevost M, Vanbelle D, et al. (1998) The Brugel package: Toward computer-aided-design of macromolecules. J Mol Graph 6: 219-219.