LEDGF dominant interference proteins demonstrate prenuclear exposure of HIV-1 integrase and synergize with LEDGF depletion to destroy viral infectivity

Journal of Virology

Volumn 85, Issue 7, 2011, Pages 3570-3583

  Meehan, Anne M ^a   Saenz, Dyana T ^a   Morrison, James ^a   Hu, Chunling ^a   Peretz, Mary ^a   Poeschla, Eric M ^a  

^a MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CORE PROTEIN; GENOMIC DNA; GREEN FLUORESCENT PROTEIN; INTEGRASE; LENS EPITHELIUM DERIVED GROWTH FACTOR;

ANTIVIRAL ACTIVITY; ARTICLE; CARBOXY TERMINAL SEQUENCE; CD4+ T LYMPHOCYTE; CELL NUCLEUS MEMBRANE; CELLULAR DISTRIBUTION; CHIMERA; CONTROLLED STUDY; CYTOPLASM; HOST CELL; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; LIFE CYCLE; LYMPHOCYTE CULTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; T LYMPHOCYTE; VIRUS DNA CELL DNA INTERACTION; VIRUS INFECTIVITY; VIRUS REPLICATION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; GENES, REPORTER; GREEN FLUORESCENT PROTEINS; HIV INTEGRASE; HIV-1; HOST-PATHOGEN INTERACTIONS; HUMANS; RECOMBINANT FUSION PROTEINS; TRANSCRIPTION FACTORS; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 79952588405     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01295-10     Document Type: Article

References (58)

1. Bao, K. K., et al. 2003. Functional oligomeric state of avian sarcoma virus integrase. J. Biol. Chem. 278:1323-1327.
2. Bartholomeeusen, K., et al. 2007. Differential interaction of HIV-1 integrase and JPO2 with the C terminus of LEDGF/p75. J. Mol. Biol. 372:407-421.
3. Bartholomeeusen, K., et al. 2009. Lens epithelium-derived growth factor/p75 interacts with the transposase-derived DDE domain of pogZ. J. Biol. Chem. 284:11467-11477.
4. Busschots, K., et al. 2005. The interaction of LEDGF/p75 with integrase is lentivirus-specific and promotes DNA binding. J. Biol. Chem. 280:17841-17847.
5. Cherepanov, P. 2007. LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res. 35:113-124. (Pubitemid 46189836)
6. Cherepanov, P., A. L. Ambrosio, S. Rahman, T. Ellenberger, and A. Engelman. 2005. Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75. Proc. Natl. Acad. Sci. U. S. A. 102:17308-17313.
7. Cherepanov, P., E. Devroe, P. A. Silver, and A. Engelman. 2004. Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional coactivator p75 (LEDGF/p75) that binds HIV-1 integrase. J. Biol. Chem. 279:48883-48892.
8. Cherepanov, P., et al. 2003. HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J. Biol. Chem. 278:372-381.
9. Cherepanov, P., et al. 2005. Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75. Nat. Struct. Mol. Biol. 12:526-532.
10. De Rijck, 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. (Pubitemid 44788865)
11. Dietz, A. B., et al. 2006. A novel source of viable peripheral blood mononuclear cells from leukoreduction system chambers. Transfusion 46:2083-2089.
12. Enarson, P., M. Enarson, R. Bastos, and B. Burke. 1998. Amino-terminal sequences that direct nucleoporin nup153 to the inner surface of the nuclear envelope. Chromosoma 107:228-236. (Pubitemid 28466461)
13. Engelman, A., and P. Cherepanov. 2008. The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathog. 4:e1000046.
14. Farnet, C. M., and F. D. Bushman. 1997. HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro. Cell 88:483-492.
15. Faure, A., et al. 2005. HIV-1 integrase crosslinked oligomers are active in vitro. Nucleic Acids Res. 33:977-986. (Pubitemid 41430518)
16. Ferris, A. L., et al. 2010. Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration. Proc. Natl. Acad. Sci. U. S. A. 107:3135-3140.
17. Ge, H., Y. Si, and R. G. Roeder. 1998. Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation. EMBO J. 17:6723-6729.
18. Gijsbers, R., et al. 2010. LEDGF hybrids efficiently retarget lentiviral integration into heterochromatin. Mol. Ther. 18:552-560.
19. Guiot, E., et al. 2006. Relationship between the oligomeric status of HIV-1 integrase on DNA and enzymatic activity. J. Biol. Chem. 281:22707-22719.
20. Hare, S., and P. Cherepanov. 2009. Review: the interaction between lentiviral integrase and LEDGF: structural and functional insights. Viruses 1:780-801.
21. Hare, S., et al. 2009. Structural basis for functional tetramerization of lentiviral integrase. PLoS Pathog. 5:e1000515.
22. Hare, S., S. S. Gupta, E. Valkov, A. Engelman, and P. Cherepanov. 2010. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 464:232-236.
23. Hare, S., et al. 2009. A novel co-crystal structure affords the design of gain-of-function lentiviral integrase mutants in the presence of modified PSIP1/LEDGF/p75. PLoS Pathog. 5:e1000259.
24. Hayouka, Z., et al. 2007. Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium. Proc. Natl. Acad. Sci. U. S. A. 104:8316-8321.
25. Hombrouck, A., et al. 2007. Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. PLoS Pathog. 3:e47.
26. Li, M., M. Mizuuchi, T. R. Burke, Jr., and R. Craigie. 2006. Retroviral DNA integration: reaction pathway and critical intermediates. EMBO J. 25:1295-1304.
27. Lin, C. W., and A. Engelman. 2003. The barrier-to-autointegration factor is a component of functional human immunodeficiency virus type 1 preintegration complexes. J. Virol. 77:5030-5036. (Pubitemid 36402856)
28. Llano, M., S. Delgado, M. Vanegas, and E. M. Poeschla. 2004. LEDGF/p75 prevents proteasomal degradation of HIV-1 integrase. J. Biol. Chem. 279:55570-55577.
29. Llano, M., J. Morrison, and E. Poeschla. 2010. Virological and cellular roles of the transcriptional coactivator LEDGF/p75. Curr. Top. Microbiol. Immunol. 339:125-146.
30. Llano, M., et al. 2006. An essential role for LEDGF/p75 in HIV integration. Science 314:461-464. (Pubitemid 44628966)
31. Llano, M., et al. 2004. LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral pre-integration complexes. J. Virol. 78:9524-9537. (Pubitemid 39096559)
32. Llano, M., 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.
33. Loewen, N., et al. 2003. FIV vectors. Methods Mol. Biol. 229:251-271.
34. Maertens, G., 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.
35. Maertens, G. N., P. Cherepanov, and A. Engelman. 2006. Transcriptional coactivator p75 binds and tethers the Myc-interacting protein JPO2 to chromatin. J. Cell Sci. 119:2563-2571. (Pubitemid 44070437)
36. Marshall, H. M., et al. 2007. Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting. PLoS One 2:e1340.
37. McDonald, D., et al. 2002. Visualization of the intracellular behavior of HIV in living cells. J. Cell Biol. 159:441-452. (Pubitemid 35332831)
38. McKee, C. J., et al. 2008. Dynamic modulation of HIV-1 integrase structure and function by cellular lens epithelium-derived growth factor (LEDGF) protein. J. Biol. Chem. 283:31802-31812.
39. Meehan, A. M., and E. M. Poeschla. 2010. Chromatin tethering and retroviral integration: recent discoveries and parallels with DNA viruses. Biochim. Biophys. Acta 1799:182-191.
40. Meehan, A. M., et al. 2009. LEDGF/p75 proteins with alternative chromatin tethers are functional HIV-1 cofactors. PLoS Pathog. 5:e1000522.
41. Miller, M. D., C. M. Farnet, and F. D. Bushman. 1997. Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition. J. Virol. 71:5382-5390.
42. Pandey, K. K., S. Sinha, and D. P. Grandgenett. 2007. Transcriptional coactivator LEDGF/p75 modulates human immunodeficiency virus type 1 integrase-mediated concerted integration. J. Virol. 81:3969-3979.
43. Poeschla, E., F. Wong-Staal, and D. Looney. 1998. Efficient transduction of nondividing cells by feline immunodeficiency virus lentiviral vectors. Nat. Med. 4:354-357.
44. Poeschla, E. M. 2008. Integrase, LEDGF/p75 and HIV replication. Cell. Mol. Life Sci. 65:1403-1424.
45. Raghavendra, N. K., and A. Engelman. 2007. LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: implications for the mechanism of viral cDNA integration. Virology 360:1-5.
46. Shun, M. C., et al. 2007. LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev. 21:1767-1778.
47. Silvers, R. M., et al. 2009. Modification of integration site preferences of an HIV-1-based vector by expression of a novel synthetic protein. Hum. Gene Ther. 21:337-349.
48. Siomi, H., and G. Dreyfuss. 1995. A nuclear localization domain in the hnRNP A1 protein. J. Cell Biol. 129:551-560.
49. Stenglein, M. D., M. B. Burns, M. Li, J. Lengyel, and R. S. Harris. APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nat. Struct. Mol. Biol. 17:222-229.
50. Turlure, F., G. Maertens, S. Rahman, P. Cherepanov, and A. Engelman. 2006. A tripartite DNA-binding element, comprised of the nuclear localization signal and two AT-hook motifs, mediates the association of LEDGF/p75 with chromatin in vivo. Nucleic Acids Res. 34:1663-1675.
51. Van Maele, B., K. Busschots, L. Vandekerckhove, F. Christ, and Z. Debyser. 2006. Cellular cofactors of HIV-1 integration. Trends Biochem. Sci. 31:98-105.
52. Vandekerckhove, L., 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. (Pubitemid 43228728)
53. Vanegas, M., et al. 2005. Identification of the LEDGF/p75 HIV-1 integraseinteraction domain and NLS reveals NLS-independent chromatin tethering. J. Cell Sci. 118:1733-1743. (Pubitemid 40691901)
54. Varadarajan, P., et al. 2005. The functionally conserved nucleoporins Nup124p from fission yeast and the human Nup153 mediate nuclear import and activity of the Tf1 retrotransposon and HIV-1 Vpr. Mol. Biol. Cell 16:1823-1838.
55. Wang, J. Y., H. Ling, W. Yang, and R. Craigie. 2001. Structure of a twodomain fragment of HIV-1 integrase: implications for domain organization in the intact protein. EMBO J. 20:7333-7343. (Pubitemid 34062324)
56. Woodward, C. L., S. Prakobwanakit, S. Mosessian, and S. A. Chow. 2009. Integrase interacts with nucleoporin NUP153 to mediate the nuclear import of human immunodeficiency virus type 1. J. Virol. 83:6522-6533.
57. Yamashita, M., and M. Emerman. 2004. Capsid is a dominant determinant of retrovirus infectivity in nondividing cells. J. Virol. 78:5670-5678. (Pubitemid 38661654)
58. Yokoyama, A., and M. L. Cleary. 2008. Menin critically links MLL proteins with LEDGF on cancer-associated target genes. Cancer Cell 14:36-46.