Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication

Journal of Virology

Volumn 78, Issue 23, 2004, Pages 12735-12746

  Lu, Richard ^a   Limón, Ana ^a,b   Devroe, Eric ^a   Silver, Pamela A ^a   Cherepanov, Peter ^a   Engelman, Alan ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; INTEGRASE; MUTANT PROTEIN; VIRUS FUSION PROTEIN;

AMINO ACID SEQUENCE; ARTICLE; CATALYSIS; CELLULAR DISTRIBUTION; ENZYME ACTIVITY; GENE DELETION; GENETIC COMPLEMENTATION; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; PHENOTYPE; PRIORITY JOURNAL; REVERSE TRANSCRIPTION; VIRUS MUTANT; VIRUS REPLICATION;

ACTIVE TRANSPORT, CELL NUCLEUS; CATALYSIS; GENE PRODUCTS, VPR; HELA CELLS; HIV INTEGRASE; HIV-1; HUMANS; MUTATION; NUCLEAR LOCALIZATION SIGNALS; TRANSCRIPTION, GENETIC; VIRUS REPLICATION;

EID: 8644226108     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.78.23.12735-12746.2004     Document Type: Article

References (68)

1. Adachi, A., H. E. Gendelman, S. Koenig, T. Folks, R. Willey, A. Rabson, and M. A. Martin. 1986. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J. Virol. 59:284-291.
2. Ansari-Lari, M. A., L. A. Donehower, and R. Gibbs. 1995. Analysis of human immunodeficiency virus type 1 integrase mutants. Virology 211:332-335.
3. Armon-Omer, A., A. Graessmann, and A. Loyter. 2004. 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. 336:1117-1128.
4. Bischerour, J., H. Leh, E. Deprez, J.-C. Brochon, and J.-F. Mouscadet. 2003. Disulfide-linked integrase oligomers involving C280 residues are formed in vitro and in vivo but are not essential for human immunodeficiency virus replication. J. Virol. 77:135-141.
5. Blaber, M., X. J. Zhang, and B. W. Matthews. 1993. Structural basis of amino acid alpha helix propensity. Science 260:1637-1640.
6. Bouyac-Bertoia, M., J. D. Dvorin, R. A. M. Fouchier, Y. Jenkins, B. E. Meyer, L. I. Wu, M. Emerman, and M. H. Malim. 2001. HIV-1 infection requires a functional integrase NLS. Mol. Cell 7:1025-1035.
7. Brown, H. E. V., H. Chen, and A. Engelman. 1999. Structure-based mutagenesis of the human immunodeficiency virus type 1 DNA attachment site: effects on integration and cDNA synthesis. J. Virol. 73:9011-9020.
8. Bukovsky, A., and H. Göttungen 1996. Lack of integrase can markedly affect human immunodeficiency virus type 1 particle production in the presence of an active viral protease. J. Virol. 70:6820-6825.
9. Cannon, P. M., E. D. Byles, S. M. Kingsman, and A. J. Kingsman. 1996. Conserved sequences in the carboxyl terminus of integrase that are essential for human immunodeficiency virus type 1 replication. J. Virol. 70:651-657.
10. Chen, H., and A. Engelman. 2001. Asymmetric processing of human immunodeficiency virus type 1 cDNA in vivo: implications for functional end coupling during the chemical steps of DNA transposition. Mol. Cell. Biol. 21:6758-6767.
11. Chen, H., S.-Q. Wei, and A. Engelman. 1999. Multiple integrase functions are required to form the native structure of the human immunodeficiency virus type I intasome. J. Biol. Chem. 274:17358-17364.
12. Cherepanov, P., G. Maertens, P. Proost, B. Devreese, J. Van Beeumen, Y. Engelborghs, E. De Clercq, and Z. Debyser. 2003. HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J. Biol. Chem. 278:372-381.
13. Collman, R., J. W. Balliet, S. A. Gregory, H. Friedman, D. L. Kolson, N. Nathanson, and A. Srinivasan. 1992. An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J. Virol. 66:7517-7521.
14. Craigie, R. 2002. Retroviral DNA integration, p. 613-630. In N. L. Craig, R. Craigie, M. Gellert, and A. M. Lambowitz (ed.), Mobile DNAII. ASM Press, Washington, D.C.
15. Depienne, C., A. Mousnier, H. Leh, E. Le Rouzic, D. Dormont, S. Benichou, and C. Dargemont. 2001. Characterization of the nuclear import pathway for HIV-1 integrase. J. Biol. Chem. 276:18102-18107.
16. Depienne, C., P. Roques, C. Creminon, L. Fritsch, R. Casseron, D. Dormont, C. Dargemont, and S. Benichou. 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.
17. Devroe, E., A. Engelman, and P. A. Silver. 2003. Intracellular transport of human immunodeficiency virus type 1 integrase. J. Cell Sci. 116:4401-4408.
18. Dvorin, J. D., P. Bell, G. G. Maul, M. Yamashita, M. Emerman, and M. H. Malim. 2002. Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. J. Virol. 76:12087-12096.
19. Dyda, F., A. B. Hickman, T. M. Jenkins, A. Engelman, R. Craigie, and D. R. Davies. 1994. Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science 266:1981-1986.
20. Engelman, A. 1999. In vivo analysis of retroviral integrase structure and function. Adv. Virus Res. 52:411-426.
21. Engelman, A. 2003. The roles of cellular factors in retroviral integration. Curr. Top. Microbiol. Immunol. 281:209-238.
22. Engelman, A., F. D. Bushman, and R. Craigie. 1993. Identification of discrete functional domains of HIV-1 integrase and their organization within an active multimeric complex. EMBO J. 12:3269-3275.
23. Engelman, A., and R. Craigie. 1992. Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. J. Virol. 66:6361-6369.
24. Engelman, A., G. Englund, J. M. Orenstein, M. A. Martin, and R. Craigie. 1995. Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J. Virol. 69:2729-2736.
25. Engelman, A., Y. Liu, H. Chen, M. Farzan, and F. Dyda. 1997. Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase. J. Virol. 71:3507-3514.
26. Esposito, D., and R. Craigie. 1999. HIV integrase structure and function. Adv. Virus Res. 52:319-333.
27. Esposito, D., and R. Craigie. 1998. Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical regions for protein-DNA interaction. EMBO J. 17:5832-5843.
28. Fassati, A., D. Gorlich, I. Harrison, L. Zaytseva, and J. M. Mingot. 2003. Nuclear import of HIV-1 intracellular reverse transcription complexes is mediated by importin 7. EMBO J. 22:3675-3685.
29. Fletcher, T. M., III, M. A. Soares, S. McPhearson, H. Hui, M. Wiskerchen, M. A. Muesing, G. M. Shaw, A. D. Leavitt, J. D. Boeke, and B. H. Hahn. 1997. Complementation of integrase function in HIV-1 virions. EMBO J. 16:5123-5138.
30. Freed, E. O., G. Englund, and M. A. Martin. 1995. Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection. J. Virol. 69:3949-3954.
31. Gallay, P., T. Hope, D. Chin, and D. Trono. 1997. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc. Natl. Acad. Sci. USA 94:9825-9830.
32. Gerton, J. L., S. Ohgi, M. Olsen, J. DeRisi, and P. O. Brown. 1998. Effects of mutations in residues near the active site of human immunodeficiency virus type 1 integrase on specific enzyme-substrate interactions. J. Virol. 72:5046-5055.
33. Hehl, E. A., P. Joshi, G. V. Kalpana, and V. R. Prasad. 2004. Interaction between human immunodeficiency virus type 1 reverse transcriptase and integrase proteins. J. Virol. 78:5056-5067.
34. Hirt, B. 1967. Selective extraction of polyoma DNA from infected mouse cell cultures. J. Mol. Biol. 26:365-369.
35. Jenkins, T. M., A. Engelman, R. Ghirlando, and R. Craigie. 1996. A soluble active mutant of HIV-1 integrase: involvement of both the core and the C-terminal domains in multimerization. J. Biol. Chem. 271:7712-7718.
36. Julias, J. G., A. L. Ferris, P. L. Boyer, and S. H. Hughes. 2001. Replication of phenotypically mixed human immunodeficiency virus type 1 virions containing catalytically active and catalytically inactive reverse transcriptase. J. Virol. 75:6537-6546.
37. Kim, S. Y., R. Byrn, J. Groopman, and D. Baltimore. 1989. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. J. Virol. 63:3708-3713.
38. Korber, B., C. Kuiken, B. Foley, B. Hahn, F. McCutchan, J. W. Mellors, and J. Sodroski. 1998. Hum. retroviruses and AIDS 1998: a compilation and analysis of nucleic acid and amino acid sequences. Theoretical Biology and Biophysics Group T-10, Los Alamos National Laboratory, Los Alamos, N.Mex.
39. Kumar, R., N. Vandegraaff, L. Mundy, C. J. Burrell, and P. Li. 2002. Evaluation of PCR-based methods for the quantitation of integrated HIV-1 DNA. J. Virol. Methods 105:233-246.
40. Leavitt, A. D., G. Robles, N. Alesandro, and H. E. Varmus. 1996. Hum. 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.
41. Leavitt, A. D., L. Shiue, and H. E. Varmus. 1993. Site-directed mutagenesis of HIV-1 integrase demonstrates differential effects on integrase functions in vitro. J. Biol. Chem. 268:2113-2119.
42. Li, L., J. M. Olvera, K. E. Yoder, R. S. Mitchell, S. L. Butler, M. Lieber, S. L. Martin, and F. D. Bushman. 2001. Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection. EMBO J. 20:3272-3281.
43. Limón, A., E. Devroe, R, Lu, H. Z. Ghory, P. A. Silver, and A. Engelman. 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.
44. Limón, A., N. Nakajima, R. Lu, H. Z. Ghory, and A. Engelman. 2002. Wild-type levels of nuclear localization and human immunodeficiency virus type 1 replication in the absence of the central DNA flap. J. Virol. 76:12078-12086.
45. Lu, R., N. Nakajima, W. Hofmann, M. Benkirane, K.-T. Jeang, J. Sodroski, and A. Engelman. 2004. Simian virus 40-based replication of catalytically inactive human immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and monocyte-derived macrophages. J. Virol. 78:658-668.
46. Maertens, G., P. Cherepanov, Z. Debyser, Y. Engelborghs, and A. Engelman. 2004. Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. J. Biol. Chem. 279: 33421-33429.
47. Maertens, G., P. Cherepanov, W. Pluymers, K. Busschots, E. De Clercq, Z. Debyser, and Y. Engelborghs. 2003. LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J. Biol. Chem. 278:33528-33539.
48. Masuda, T., V. Planelles, P. Krogstad, and I. S. Chen. 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.
49. Myers, J. K., C. N. Pace, and J. M. Scholtz. 1997. A direct comparison of helix propensity in proteins and peptides. Proc. Natl. Acad. Sci. USA 94: 2833-2837.
50. Nakajima, N., R. Lu, and A. Engelman. 2001. Hum. immunodeficiency virus type 1 replication in the absence of integrase-mediated DNA recombination: definition of permissive and nonpermissive T-cell lines. J. Virol. 75:7944-7955.
51. Petit, C., O. Schwartz, and F. Mammano. 2000. The karyophilic properties of human immunodeficiency virus type 1 integrase are not required for nuclear import of proviral DNA. J. Virol. 74:7119-7126.
52. Petit, C., O. Schwartz, and F. Mammano. 1999. Oligomerization within virions and subcellular localization of human immunodeficiency virus type 1 integrase. J. Virol. 73:5079-5088.
53. Piller, S. C., L. Caly, and D. A. Jans. 2003. Nuclear import of the preintegration complex (PIC): the Achilles heel of HIV? Curr. Drug Targets 4:409-429.
54. Pluymers, W., P. Cherepanov, D. Schols, E. De Clercq, and Z. Debyser. 1999. Nuclear localization of human immunodeficiency virus type 1 integrase expressed as a fusion protein with green fluorescent protein. Virology 258:327-332.
55. Priet, S., J.-M. Navarro, G. Querat, and J. Sire. 2003. Reversion of the lethal phenotype of an HIV-1 integrase mutant virus by overexpression of the same integrase mutant protein. J. Biol. Chem. 278:20724-20730.
56. Stevenson, M. 2002. Molecular biology of lentivirus-mediated gene transfer. Curr. Top. Microbiol. Immunol. 261:1-30.
57. Telesnitsky, A., and S. P. Goff. 1997. Reverse transcriptase and the generation of retroviral DNA, p. 121-160. In J. M. Coffin, S. H. Hughes, and H. E. Varmus (ed.), Retroviruses. Cold Spring Harbor Laboratory Press, Plainview, N.Y.
58. Tsurutani, N., M. Kubo, Y. Maeda, T. Ohashi, N. Yamamoto, M. Kannagi, and T. Masuda. 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. 74:4795-1806.
59. Turlure, F., E. Devroe, P. A. Silver, and A. Engelman. 2004. Hum. cell proteins and human immunodeficiency virus DNA integration. Front. Biosci. 9:3187-3208.
60. van Gent, D. C., A. A. M. O. Groeneger, and R. H. A. Plasterk. 1992. Mutational analysis of the integrase protein of human immunodeficiency virus type 2. Proc. Natl. Acad. Sci. USA 89:9598-9602.
61. van Gent, D. C., C. Vink, A. A. M. O. Groeneger, and R. H. A. Plasterk. 1993. Complementation between HIV integrase proteins mutated in different domains. EMBO J. 12:3261-3267.
62. Wiskerchen, M., and M. A. Muesing. 1995. Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells. J. Virol. 69:376-386.
63. Wu, X., H. Liu, H. Xiao, J. A. Conway, E. Hehl, G. V. Kalpana, V. Prasad, and J. C. Kappes. 1999. Hum. immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. J. Virol. 73:2126-2135.
64. Wu, X., H. Liu, H. Xiao, J. A. Conway, E. Hunter, and J. C. Kappes. 1997. Functional RT and IN incorporated into HIV-1 particles independently of the Gag/Pol precursor protein. EMBO J. 16:5113-5122.
65. Wu, Y., and J. W. Marsh. 2003. Early transcription from nonintegrated DNA in human immunodeficiency virus infection. J. Virol. 77:10376-10382.
66. Yee, J., A. Miyanohara, P. LaPorte, K. Bouic, J. C. Burns, and T. Friedmann. 1994. A general method for the generation of high-titer, pantropic retroviral vectors: highly efficient infection of primary hepatocytes. Proc. Natl. Acad. Sci. USA 91:9564-9568.
67. Zack, J. A., S. J. Arrigo, S. R. Weitsman, A. S. Go, A. Haislip, and I. S. Chen. 1990. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61:213-222.
68. Zhu, K., C. Dobard, and S. A. Chow. 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.