Non-enzymatic functions of retroviral integrase: The next target for novel anti-HIV drug development

Frontiers in Microbiology

Volumn 2, Issue OCT, 2011, Pages

  Masuda, Takao ^a  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

Author keywords

Gemin2; HIV 1; Intasome; Integrase; Pol; Reverse transcriptase; Reverse transcription

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN SPUMARETROVIRUS; SPUMAVIRUS;

EID: 84875545671     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2011.00210     Document Type: Review

References (53)

1. Al-Mawsawi, L. Q., and Neamati, N. (2007). Blocking interactions between HIV-1 integrase and cellular cofactors: an emerging antiretroviral strategy. Trends Pharmacol. Sci. 28, 526-535.
2. Briones, M. S., Dobard, C. W., and Chow, S. A. (2010). Role of human immunodeficiency virus type 1 integrase in uncoating of the viral core. J. Virol. 84, 5181-5190.
3. Buhler,D., Raker,V., Luhrmann, R., and Fischer, U. (1999). Essential role for the tudor domain of SMNin spliceosomal U snRNP assembly: implications for spinal muscular atrophy. Hum. Mol. Genet. 8, 2351-2357.
4. Burke, C. J., Sanyal, G., Bruner, M. W., Ryan, J. A., Lafemina, R. L., Robbins, H. L., Zeft, A. S., Middaugh, C. R., andCordingley,M. G. (1992). Structural implications of spectroscopic characterization of a putative zinc finger peptide from HIV-1 integrase. J. Biol. Chem. 267, 9639-9644.
5. Bushman, F. D., Engelman, A., Palmer, I., Wingfield, P., and Craigie, R. (1993). Domains of the integrase protein of human immunodeficiency virus type 1 responsible for polynucleotidyl transfer and zinc binding. Proc. Natl. Acad. Sci. U.S.A. 90, 3428-3432.
6. Cai, M., Zheng, R., Caffrey, M., Craigie, R., Clore, G. M., andGronenborn,A. M. (1997). Solution structure of the N-terminal zinc binding domain of HIV-1 integrase. Nat. Struct. Biol. 4, 567-577.
7. Chen, J. C., Krucinski, J., Miercke, L. J., Finer-Moore, J. S., Tang,A. H., Leavitt, A. D., and Stroud, R. M. (2000). Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proc. Natl. Acad. Sci. U.S.A. 97, 8233-8238.
8. Cherepanov, P., Maertens, G., Proost, P., Devreese, B., Van Beeumen, J., Engelborghs, Y., De Clercq, E., and Debyser, Z. (2003). HIV-1 integrase formsstable tetramers and associates with LEDGF/p75 protein in human cells. J. Biol. Chem. 278, 372-381.
9. Cherepanov, P., Maertens, G. N., and Hare, S. (2011). Structural insights into the retroviral DNA integration apparatus. Curr. Opin. Struct. Biol. 21, 249-256.
10. Craigie, R. (2010). Structural biology: when four become one. Nature 464, 167-168.
11. Dobard, C. W., Briones, M. S., and Chow, S.A. (2007).Molecular mechanisms by which human immunodeficiency virus type 1 integrase stimulates the early steps of reverse transcription. J. Virol. 81, 10037-10046.
12. Dyda, F., Hickman, A. B., Jenkins, T. M., Engelman, A., Craigie, R., and Davies, D. R. (1994). Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science 266, 1981-1986.
13. Eijkelenboom, A. P., Lutzke, R. A., Boelens, R., Plasterk, R. H., Kaptein, R., and Hard, K. (1995). The DNAbinding domain of HIV-1 integrase has an SH3-like fold. Nat. Struct. Biol. 2, 807-810.
14. Ellison, V., Gerton, J., Vincent, K. A., and Brown, P. O. (1995). An essential interaction between distinct domains of HIV-1 integrase mediates assembly of the activemultimer. J. Biol. Chem. 270, 3320-3326.
15. Engelman, A., and Craigie, R. (1992). Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. J. Virol. 66, 6361-6369.
16. Engelman, A., Englund, G., Orenstein, J. M., Martin, M. A., and Craigie, R. (1995).Multiple effects ofmutations in human immunodeficiency virus type 1 integrase on viral replication. J. Virol. 69, 2729-2736.
17. Fischer, U., Liu, Q., and Dreyfuss, G. (1997). The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell 90, 1023-1029.
18. Gallay, P., Hope, T., Chin, D., and Trono, D. (1997). HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc. Natl. Acad. Sci. U.S.A. 94, 9825-9830.
19. Hamamoto, S., Nishitsuji, H., Amagasa, T., Kannagi, M., and Masuda, T. (2006). Identification of a novel human immunodeficiency virus type 1 integrase interactor, Gemin2, that facilitates efficient viral cDNA synthesis in vivo. J. Virol. 80, 5670-5677.
20. Hare, S., DiNunzio, F., Labeja, A.,Wang, J., Engelman, A., and Cherepanov, P. (2009a). Structural basis for functional tetramerization of lentiviral integrase. PLoS Pathog. 5, e1000515. doi:10.1371/journal.ppat.1000515
21. Hare, S., Shun, M. C., Gupta, S. S., Valkov, E., Engelman, A., and Cherepanov, P. (2009b). 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. doi:10.1371/journal.ppat.1000259
22. Hare, S., Gupta, S. S., Valkov, E., Engelman, A., and Cherepanov, P. (2010). Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 464, 232-236.
23. Ikeda, T., Nishitsuji, H., Zhou, X., Nara, N., Ohashi, T., Kannagi, M., and Masuda, T. (2004). Evaluation of the functional involvement of human immunodeficiency virus type 1 integrase in nuclear import of viral cDNA during acute infection. J. Virol. 78, 11563-11573.
24. Jablonka, S., Bandilla, M., Wiese, S., Buhler, D., Wirth, B., Sendtner, M., and Fischer, U. (2001). Coregulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Hum. Mol. Genet. 10, 497-505.
25. Katz, R. A., and Skalka, A. M. (1994). The retroviral enzymes. Annu. Rev. Biochem. 63, 133-173.
26. Krishnan, L., Li, X., Naraharisetty, H. L., Hare, S., Cherepanov, P., and Engelman, A. (2010). Structurebased modeling of the functional HIV-1 intasome and its inhibition. Proc. Natl. Acad. Sci. U.S.A. 107, 15910-15915.
27. Kulkosky, J., Jones, K. S., Katz, R. A., Mack, J. P., and Skalka, A. M. (1992). 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. 12, 2331-2338.
28. LaFemina, R. L., Schneider, C. L., Robbins, H. L., Callahan, P. L., Legrow, K., Roth, E., Schleif, W. A., and Emini, E. A. (1992). Requirement of active human immunodeficiency virus type 1 integrase enzyme for productive infection of human T-lymphoid cells. J.Virol. 66, 7414-7419.
29. Leavitt, A. D., Robles, G., Alesandro, N., and Varmus, H. E. (1996). Human immunodeficiency virus type 1 integrase mutants retain in vitro integrase activity yet fail to integrate viral DNA efficiently during infection. J. Virol. 70, 721-728.
30. Li, M., Mizuuchi, M., Burke, T. R. Jr., and Craigie, R. (2006). Retroviral DNA integration: reaction pathway and critical intermediates. EMBO J. 25, 1295-1304.
31. Li, X., Krishnan, L., Cherepanov, P., and Engelman, A. (2011). Structural biology of retroviral DNA integration. Virology 411, 194-205.
32. Liu, Q., Fischer, U.,Wang, F., and Dreyfuss, G. (1997). The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell 90, 1013-1021.
33. Lodi, P. J., Ernst, J. A., Kuszewski, J., Hickman, A. B., Engelman, A., Craigie, R., Clore, G. M., and Gronenborn, A. M. (1995). Solution structure of the DNA binding domain of HIV-1 integrase. Biochemistry 34, 9826-9833.
34. Lu, R., Ghory, H. Z., and Engelman, A. (2005). Genetic analyses of conserved residues in the carboxylterminal domain of human immunodeficiency virus type 1 integrase. J. Virol. 79, 10356-10368.
35. Luo, Y., and Muesing, M. A. (2010). Prospective strategies for targeting HIV-1 integrase function. Future Med. Chem. 2, 1055-1060.
36. Maertens, G., Cherepanov, P., Debyser, Z., Engelborghs, Y., and 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.
37. Maertens, G., Cherepanov, P., Pluymers, W., Busschots, K., De Clercq, E., Debyser, Z., and Engelborghs, Y. (2003). LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J. Biol. Chem. 278, 33528-33539.
38. Masuda, T., Planelles, V., Krogstad, P., and Chen, I. S. (1995). Genetic analysis of human immunodeficiency virus type 1 integrase and the U3 att site: unusual phenotype of mutants in the zinc finger-like domain. J. Virol. 69, 6687-6696.
39. Meister, G., Buhler, D., Pillai, R., Lottspeich, F., and Fischer,U. (2001). A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs. Nat. Cell Biol. 3, 945-949.
40. Metifiot, M., Marchand, C., Maddali, K., and Pommier, Y. (2010). Resistance to integrase inhibitors. Viruses 2, 1347-1366.
41. Mohammed, K. D., Topper, M. B., and Muesing, M. A. (2011). Sequential deletion of the integrase (Gag-Pol) carboxyl terminus reveals distinct phenotypic classes of defective HIV-1. J. Virol. 85, 4654-4666.
42. Nakamura, T., Masuda, T., Goto, T., Sano, K., Nakai, M., and Harada, S. (1997). Lack of infectivity of HIV-1 integrase zinc finger-like domain mutant with morphologically normal maturation. Biochem. Biophys. Res. Commun. 239, 715-722.
43. Nishitsuji, H., Hayashi, T., Takahashi, T., Miyano, M., Kannagi, M., and Masuda, T. (2009). Augmentation of reverse transcription by integrase through an interactionwith host factor, SIP1/Gemin2 Is critical for HIV-1 infection. PLoS ONE 4, e7825. doi:10.1371/journal.pone.0007825
44. Nomura, Y., Masuda, T., and Kawai, G. (2006). Structural analysis of a mutant of the HIV-1 integrase zinc finger domain that forms a single conformation. J. Biochem. 139, 753-759.
45. Nymark-McMahon, M. H., Beliakova-Bethell, N. S., Darlix, J. L., Le Grice, S. F., and Sandmeyer, S. B. (2002). Ty3 integrase is required for initiation of reverse transcription. J.Virol. 76, 2804-2816.
46. Nymark-McMahon, M. H., and Sandmeyer, S. B. (1999). Mutations in nonconserved domains of Ty3 integrase affectmultiple stages of theTy3 life cycle. J. Virol. 73, 453-465.
47. Shun, M. C., Raghavendra, N. K., Vandegraaff, N., Daigle, J. E., Hughes, S., Kellam, P., Cherepanov, P., and Engelman, A. (2007). LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev. 21, 1767-1778.
48. Summa, V., Petrocchi, A., Bonelli, F., Crescenzi, B., Donghi, M., Ferrara, M., Fiore, F., Gardelli, C., Gonzalez Paz, O., Hazuda, D. J., Jones, P., Kinzel, O., Laufer, R., Monteagudo, E., Muraglia, E., Nizi, E., Orvieto, F., Pace, P., Pescatore, G., Scarpelli, R., Stillmock, K., Witmer, M. V., and Rowley, M. (2008). Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIVAIDS infection. J. Med. Chem. 51, 5843-5855.
49. Tsurutani, N., Kubo, M., Maeda, Y., Ohashi, T., Yamamoto, N., Kannagi, M., and Masuda, T. (2000). Identification of critical amino acid residues in human immunodeficiency virus type 1 IN required for efficient proviral DNA formation at steps prior to integration in dividing and nondividing cells. J. Virol. 74, 4795-4806.
50. Wang, J. Y., Ling, H., Yang, W., and Craigie, R. (2001). Structure of a two-domain fragment of HIV-1 integrase: implications for domain organization in the intact protein. EMBO J. 20, 7333-7343.
51. Wilkinson, T. A., Januszyk, K., Phillips, M. L., Tekeste, S. S., Zhang, M., Miller, J. T., Le Grice, S. F., Clubb, R. T., and Chow, S. A. (2009). Identifying and characterizing a functional HIV-1 reverse transcriptase-binding site on integrase. J. Biol. Chem. 284, 7931-7939.
52. Wu, X., Liu, H., Xiao, H., Conway, J. A., Hehl, E., Kalpana, G. V., Prasad, V., and Kappes, J. C. (1999). Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. J. Virol. 73, 2126-2135.
53. Zhu, K., Dobard, C., and Chow, S. A. (2004). Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J. Virol. 78, 5045-5055.