In search of authentic inhibitors of HIV-1 integration

Antiviral Chemistry and Chemotherapy

Volumn 13, Issue 1, 2002, Pages 1-15

  Debyser, Zeger ^a   Cherepanov, Peter ^a   Van Maele, Bénédicte ^a   De Clercq, Erik ^a   Witvrouw, Myriam ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

AIDS; Antiviral; HIV; Integrase

Indexed keywords

ANTIVIRUS AGENT; INTEGRASE; PROTEINASE; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; VIRUS ENZYME;

ANTIVIRAL ACTIVITY; CATALYSIS; CHROMOSOME; DRUG ACTIVITY; DRUG POTENCY; ENZYME INHIBITION; GENOME; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PRIORITY JOURNAL; REVIEW; TREATMENT PLANNING; VIRUS INHIBITION; VIRUS REPLICATION; VIRUS STRAIN;

EID: 0036462265     PISSN: 09563202     EISSN: None     Source Type: Journal    
DOI: 10.1177/095632020201300101     Document Type: Review

References (108)

1. Baekelandt V, Claeys A, Cherepanov P, De Clercq E, De Strooper B, Nuttin B & Debyser Z 2000 DNA-dependent protein kinase is not required for efficient lentivirus integration. Journal of Virology 74:11278-11285.
2. Barsov EV, Huber WE, Marcotrigiano J, Clark PK, Clark AD, Arnold E & Hughes SH (1996) Inhibition of human immunodeficiency virus type 1 integrase by the Fab fragment of a specific monoclonal antibody suggests that different multimerization states are required for different enzymatic functions. Journal of Virology 70:4484-4494.
3. Bouyac-Bertoia M, Dvorin JD, Fouchier RA, Jenkins Y, Meyer BE, Wu LI, Emerman M & Malim MH (2001) HIV-1 infection requires a functional integrase NLS. Molecular Cell 7:1025-1035.
4. Brin E, Yi J, Skalka AM & Leis J (2000) Modeling the late steps in HIV-1 retroviral integrase-catalyzed DNA integration. Journal of Biological Chemistry 275:39287-39295.
5. Brooun A, Richman DD & Kornbluth RS (2001) HIV-1 preintegration complexes preferentially integrate into longer target DNA molecules in solution as detected by a sensitive, polymerase chain reaction-based integration assay. Journal of Biological Chemistry 276:46946-46952.
6. Brown PO, Bowerman B, Varmus HE & Bishop JM (1987) Correct integration of retroviral DNA in vitro. Cell 49:347-356.
7. Brown PO (1997) Integration of retroviral DNA. Current Topics in Microbiological Immunology 157:19-47.
8. Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S & Stevenson M (1992) Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proceedings of the National Academy of Sciences USA 89:6580-6584.
9. Bukrinsky MI, Sharova N, McDonald TL, Pushkarskaya T, Tarpley WG & Stevenson M (1993) Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection. Proceedings of the National Academy of Sciences USA 90:6125-6129.
10. Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M & Stevenson M (1993) A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365:666-669.
11. Burke CJ, Sanyal G, Bruner MW, Ryan JA, LaFemina RL, Robbins HL, Zeft AS, Middaugh CR & Cordingley MG (1992) Structural implications of spectroscopic characterization of a putative zinc finger peptide from HIV-1 integrase. Journal of Biological Chemistry 267:9639-9644.
12. Bushman FD, Fujiwara T & Craigie R (1990) Retroviral DNA integration directed by HIV integration protein in vitro. Science 249:1555-1558.
13. Bushman FD, Engelman A, Palmer I, Wingfield P & Craigie R (1993) Domains of the integrase protein of human immunodeficiency virus type 1 responsible for polynucleotidyl transfer and zinc binding. Proceedings of the National Academy of Sciences USA 90:3428-3432.
14. Butler SL, Hansen MS & Bushman FD (2001) A quantitative assay for HIV DNA integration in vivo. Nature Medicine 7:631-634.
15. Cai M, Zheng R, Caffrey M, Craigie R, Clore GM & Gronenborn AM (1997) Solution structure of the N-terminal zinc binding domain of HIV-1 integrase. Nature Structural Biology 4:567-577.
16. Cai M, Huang Y, Zheng R, Wei SQ, Ghirlando R, Lee MS, Craigie R, Gronenborn AM & Clore GM (1998) Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration. Nature Structural Biology 5:903-909.
17. Cannon PM, Byles ED, Kingsman SM & Kingsman AJ (1996) Conserved sequences in the carboxyl terminus of integrase that are essential for human immunodeficiency virus type 1 replication. Journal of Virology 70:651-657.
18. Chen H & Engelman A (1998) The barrier-to-autointegration protein is a host factor for HIV type 1 integration. Proceedings of the National Academy of Sciences USA 95:15270-15274.
19. Chen JC, Krucinski J, Miercke LJ, Finer-Moore JS, Tang AH, Leavitt AD & Stroud RM (2000) Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proceedings of the National Academy of Sciences USA 97:8233-8238.
20. Cherepanov P, Este JA, Rando RF, Ojwang JO, Reekmans G, Steinfeld R, David G, De Clercq E & Debyser Z (1997) Mode of interaction of G-quartets with the integrase of human immunodeficiency virus type 1. Molecular Pharmacology 52:771-780.
21. Chow SA, Vincent KA, Ellison V & Brown PO (1992) Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus. Science 255:723-726.
22. Craigie R, Fujiwara T & Bushman F (1990) The IN protein of Moloney murine leukemia virus processes the viral DNA ends and accomplishes their integration in vitro. Cell 62:829-837.
23. Daniel R, Katz RA & Skalka AM (1999) A role for DNA-PK in retroviral DNA integration. Science 284:644-647.
24. Davies JFD, Hostomska Z, Hostomsky Z, Jordan SR & Matthews DA (1991) Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 252:88-95.
25. De Clercq E (1995) Toward improved anti-HIV chemotherapy: therapeutic strategies for intervention with HIV infections. Journal of Medicinal Chemistry 38:2491-2517.
26. De Clercq E (2001) New developments in anti-HIV chemotherapy. Current Medicinal Chemistry 8:1543-1572.
27. Debyser Z, Cherepanov P, Pluymers W & De Clercq E (2001) Assays for the evaluation of HIV-1 integrase inhibitors. In Methods in Molecular Biology; pp. 139-155. Edited by CH Schein. Totowa, New Jersey: Humana Press.
28. Depienne C, Roques P, Creminon C, Fritsch L, Casseron R, Dormont D, Dargemont C & Benichou S (2000) Cellular distribution and karyophilic properties of matrix, integrase, and Vpr proteins from the human and simian immunodeficiency viruses. Experimental Cell Research 260:387-395.
29. Depienne C, Mousnier A, Leh H, Le Rouzic E, Dormont D, Benichou S & Dargemont C (2001) Characterization of the nuclear import pathway for HIV-1 integrase. Journal of Biological Chemistry 276:18102-18107.
30. Dyda F, Hickman AB, Jenkins TM, Engelman A, Craigie R & Davies DR (1994) Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynudeotidyl transferases. Science 266:1981-1986.
31. Eijkelenboom AP, Lutzke RA, Boelens R, Plasterk RH, Kaptein R & Hard K (1995) The DNA-binding domain of HIV-1 integrase has an SH3-like fold. Nature Structural Biology 2:807-810.
32. Ellison V, Abrams H, Roe T, Lifson J & Brown P (1990) Human immunodeficiency virus integration in a cell-free system. Journal of Virology 64:2711-2715.
33. Engelman A & Craigie R (1992) Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. Journal of Virology 66:6361-6369.
34. Engelman A, Englund G, Orenstein JM, Martin MA & Craigie R (1995) Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. Journal of Virology 69:2729-2736.
35. Espeseth AS, Felock P, Wolfe A, Witmer M, Grobler J, Anthony N, Egbertson M, Melamed JY, Young S, Hamill T, Cole JL & Hazuda DJ (2000) HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase. Proceedings of the National Academy of Sciences USA 97:11244-11249.
36. Esté JA, Cabrera C, Schols D, Cherepanov P, Gutierrez A, Witvrouw M, Pannecouque C, Debyser Z, Rando RF, Clotet B, Desmyter J & De Clercq E (1998) Human immunodeficiency virus glycoprotein gpl20 as the primary target for the antiviral action of AR177 (Zintevir). Molecular Pharmacology 53:340-345.
37. Farnet CM & Haseltine WA (1990) Integration of human immunodeficiency virus type 1 DNA in vitro. Proceedings of the National Academy of Sciences USA 87:4164-4168.
38. Farnet CM, Wang B, Lipford JR & Bushman FD (1996) Differential inhibition of HIV-1 preintegration complexes and purified integrase protein by small molecules. Proceedings of the National Academy of Sciences USA 93:9742-9747.
39. Farnet CM & Bushman FD (1996) HIV cDNA integration: molecular biology and inhibitor development. AIDS 10(Suppl. A):S3-S11.
40. Farnet CM & Bushman FD (1997) HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro. Cell 88:483-492.
41. Fesen MR, Pommier Y, Leteurtre F, Hiroguchi S, Yung J & Kohn KW (1994) Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds. Biochemical Pharmacology 48:595-608.
42. Fouchier RA, Meyer BE, Simon JH, Fischer U, Albright AV, Gonzalez-Scarano F & Malim MH (1998) Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex. Journal of Virology 72:6004-6013.
43. Friedler A, Zakai N, Karni O, Broder YC, Baraz L, Kotler M, Loyter A & Gilon C (1998) Backbone cyclic peptide, which mimics the nuclear localization signal of human immunodeficiency virus type 1 matrix protein, inhibits nuclear import and virus production in nondividing cells. Biochemistry 37:5616-5622.
44. Gallay P, Swingler S, Song J, Bushman F & Trono D (1995) HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 83:569-576.
45. Gallay P, Hope T, Chin D & Trono D (1997) HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proceedings of the National Academy of Sciences USA 94:9825-9830.
46. Goldgur Y, Craigie R, Cohen GH, Fujiwara T, Yoshinaga T, Fujishita T, Sugimoto H, Endo T, Murai H & Davies DR (1999) Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design. Proceedings of the NationalAcademy of Sciences USA 96:13040-13043.
47. Goulaouic H & Chow SA (1996) Directed integration of viral DNA mediated by fusion proteins consisting of human immunodeficiency virus type 1 integrase and Escherichia coli LexA protein. Journal of Virology 70:37-46.
48. Ha HC, Juluri K, Zhou Y, Leung S, Hermankova M, Snyder SH (2001) Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration. Proceedings of the NationalAcademy of Sciences USA 98:3364-3368.
49. Hansen MS, Smith 3rd GJ, Kafri T, Molteni V, Siegel JS & Bushman FD (1999) Integration complexes derived from HIV vectors for rapid assays in vitro. Nature Biotechnology 17:578-582.
50. Hazuda D, Blau CU, Felock P, Hastings J, Pramanik B, Wolfe A, Bushman F, Farnet C, Goetz M, Williams M, Silverman K, Lingham R & Singh S (1999) Isolation and characterization of novel human immunodeficiency virus integrase inhibitors from fungal metabolites. Antiviral Chemistry & Chemotherapy 10:63-70.
51. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, Espeseth A, Gabryelski L, Schleif W, Blau C & Miller MD (2000) Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 287:646-650.
52. Heinzinger NK, Bukinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA, Gendelman HE, Ratner L, Stevenson M & Emerman M (1994) The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proceedings of the National Academy of Sciences USA 91:7311-7315.
53. Kalpana GV & Goff SP (1993) Genetic analysis of homomeric interactions of human immunodeficiency virus type 1 integrase using the yeast two-hybrid system. Proceedings of the National Academy of Sciences USA 90:10593-10597.
54. Kalpana GV, Marmon S, Wang W, Crabtree GR & Goff SP (1994) Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science 266:2002-2006.
55. Kalpana GV, Reicin A, Cheng GS, Sorin M, Paik S & Goff SP (1999) Isolation and characterization of an oligomerization-negative mutant of HIV-1 integrase. Virology 259:274-285.
56. Katz RA, Merkel G, Kulkosky J, Leis J & Skalka AM (1990) The avian retroviral IN protein is both necessary and sufficient for integrative recombination in vitro. Cell 63:87-95.
57. Katz RA, Merkel G, Skalka AM (1996) Targeting of retroviral integrase by fusion to a heterologous DNA binding domain: in vitro activities and incorporation of a fusion protein into viral particles. Virology 217:178-190.
58. Khan E, Mack JP, Katz RA, Kulkosky J & Skalka AM (1991) Retroviral integrase domains: DNA binding and the recognition of LTR sequences [published erratum appears in Nucleic Acids Res 1991 Mar 25;19(6):1358]. Nucleic Acids Research 19:851-860.
59. King PJ & Robinson WE Jr (1998) Resistance to the anti-human immunodeficiency virus type 1 compound L- chicoric acid results from a single mutation at amino acid 140 of integrase. Journal of Virology 72:8420-8424.
60. Kulkosky J, Jones KS, Katz RA, Mack JP & Skalka AM (1992) Residues critical for retroviral integrative recombination in a region that is highly conserved among retroviral/retrotransposon integrases and bacterial insertion sequence transposases. Molecular and Cellular Biology 12:2331-2338.
61. LaFemina RL, Schneider CL, Robbins HL, Callahan PL, LeGrow K, Roth E, Schleif WA & Emini EA (1992) Requirement of active human immunodeficiency virus type 1 integrase enzyme for productive infection of human T-lymphoid cells. Journal of Virology 66:7414-7419.
62. Leavitt AD, Shiue L & Varmus HE (1993) Site-directed mutagenesis of HIV-1 integrase demonstrates differential effects on integrase functions in vitro. Journal of Biological Chemistry 268:2113-2119.
63. Lee MS & Craigie R (1998) A previously unidentified host protein protects retroviral DNA from autointegration. Proceedings of the National Academy of Sciences USA 95:1528-1533.
64. Lee SP, Xiao J, Knutson JR, Lewis MS & Han MK (1997) Zn2+ promotes the self-association of human immunodeficiency virus type-1 integrase in vitro. Biochemistry 36:173-180.
65. Lee-Huang S, Huang PL, Huang PL, Bourinbaiar AS, Chen HC & Kung HF (1995) Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31. Proceedings of the National Academy of Sciences USA 92:8818-8822.
66. Lodi PJ, Ernst JA, Kuszewski J, Hickman AB, Engelman A, Craigie R, Clore GM & Gronenborn AM (1995) Solution structure of the DNA binding domain of HIV-1 integrase. Biochemistry 34:9826-9833.
67. Lutzke RA, Vink C & Plasterk RH (1994) Characterization of the minimal DNA-binding domain of the HIV integrase protein. Nucleic Acids Research 22:4125-4131.
68. 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. Journal of Virology 72:4841-4848.
69. Marchand C, Neamati N & Pommier Y (2001) In vitro human immunodeficiency virus type 1 integrase assays. Methods in Enzymology 340:624-633.
70. Mazumder A, Neamati N, Ojwang JO, Sunder S, Rando RF & Pommier Y (1996) Inhibition of the human immunodeficiency virus type 1 integrase by guanosine quartet structures. Biochemistry 35:13762-13771.
71. Miller MD, Bor YC and Bushman F (1995) Target DNA capture by HIV-1 integration complexes. Current Biology 5:1047-1056.
72. Morozov A, Yung E & Kalpana GV (1998) Structure-function analysis of integrase interactor 1/hSNF5L1 reveals differential properties of two repeat motifs present in the highly conserved region. Proceedings of the National Academy of Sciences USA 95:1120-1125.
73. Mumm SR & Grandgenett DP (1991) Defining nucleic acid-binding properties of avian retrovirus integrase by deletion analysis. Journal of Virology 65:1160-1167.
74. Neamati N, Hong H, Sunder S, Milne GW & Pommier Y (1997) Potent inhibitors of human immunodeficiency virus type 1 integrase: identification of a novel four-point pharmacophore and tetracyclines as novel inhibitors. Molecular Pharmacology 52:1041-1055.
75. Neamati N, Hong H, Owen JM, Sunder S, Winslow HE, Christensen JL, Zhao H, Burke TR Jr, Milne GW & Pommier Y (1998) Salicylhydrazine-containing inhibitors of HIV-1 integrase: implication for a selective chelation in the integrase active site. Journal of Medicinal Chemistry 41:3202-3209.
76. Neamati N, Mazumder A, Sunder S, Owen JM, Tandon M, Lown JW, Pommier Y (1998) Highly potent synthetic polyamides, bisdistamycins, and lexitropsins as inhibitors of human immunodeficiency virus type 1 integrase. Molecular Pharmacology 54:280-290.
77. Neamati N, Turpin JA, Winslow HE, Christensen JL, Williamson K, Orr A, Rice WG, Pommier Y, Garofalo A, Brizzi A, Campiani G, Fiorini I & Nacci V (1999) Thiazolothiazepine inhibitors of HIV-1 integrase. Journal of Medicinal Chemistry 42:3334-3341.
78. Neamati N, Marchand C & Pommier Y (2000) HIV-1 integrase inhibitors: past, present, and future. Advances in Pharmacology 49:147-165.
79. Ojwang JO, Buckheit RW, Pommier Y, Mazumder A, De Vreese K, Este JA, Reymen D, Pallansch LA, Lackman-Smith C, Wallace TL, De Clereq E, McGrath MS & Rando RF (1995) T30177, an oligonucleotide stabilized by an intramolecular guanosine octet, is a potent inhibitor of laboratory strains and clinical isolates of human immunodeficiency virus type 1. Antimicrobial Agents and Chemotherapy 39:2426-2435.
80. Petit C, Schwartz O & Mammano F (2000) The karyophilic properties of human immunodeficiency virus type 1 integrase are not required for nuclear import of proviral DNA. Journal of Virology 74:7119-7126.
81. 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.
82. Pluymers W, Neamati N, Pannecouque C, Fikkert V, Marchand C, Burke TR Jr, Pommier Y, Schols D, De Clercq E, Debyser Z & Witvrouw M (2000) Viral Entry as the Primary Target for the Anti-HIV Activity of Chicoric Acid and Its Tetra-Acetyl Esters. Molecular Pharmacology 58:641-648.
83. Pommier Y & Neamati N (1999) Inhibitors of human immunodeficiency virus integrase. Advances in Virus Research 52:427-458.
84. Pommier Y, Marchand C & Neamati N (2000) Retroviral integrase inhibitors year 2000: update and perspectives. Antiviral Research 47:139-148.
85. Popov S, Dubrovsky L, Lee MA, Pennathur S, Haffar O, aL-Abed Y, Tonge P, Ulrich P, Rexach M, Blobel G, Cerami A & Bukrinsky M (1996) Critical role of reverse transcriptase in the inhibitory mechanism of CNI-H0294 on HIV-1 nuclear translocation. Proceedings of the National Academy of Sciences USA 93:11859-11864
86. Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G & Bukrinsky M (1998) Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. The EMBO Journal 17:909-917.
87. Rando RF, Ojwang J, Elbaggari A, Reyes GR, Tinder R, McGrath MS & Hogan ME (1995) Suppression of human immunodeficiency virus type 1 activity in vitro by oligonucleotides which form intramolecular tetrads. Journal of Biological Chemistry 270:1754-1760.
88. Rice P, Craigie R & Davies DR (1996) Retroviral integrases and their cousins. Current Opinion in Structural Biology 6:76-83.
89. Rice P & Mizuuchi K (1995) Structure of the bacteriophage Mu transposase core: a common structural motif for DNA transposition and retroviral integration. Cell 82:209-220.
90. Robinson WE Jr, Cordeiro M, Abdel-Malek S, Jia Q, Chow SA, Reinecke MG & Mitchell WM (1996a). Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase. Molecular Pharmacology 50:846-855.
91. Robinson WE Jr, Reinecke MG, Abdel-Malek S, Jia Q & Chow SA (1996b) Inhibitors of HIV-1 replication that inhibit HIV integrase. Proceedings of the National Academy of Sciences USA 93:6326-6331.
92. Sherman PA & Fyfe JA (1990) Human immunodeficiency virus integration protein expressed in Escherichia coli possesses selective DNA cleaving activity. Proceedings of the National Academy of Sciences USA 87:5119-5123.
93. Tasara T, Maga G, Hottiger MO & Hubscher U (2001) HIV-1 reverse transcriptase and integrase enzymes physically interact and inhibit each other. FEBS Letters 507:39-44.
94. Turelli P, Doucas V, Craig E, Mangeat B, Klages N, Evans R, Kalpana G & Trono D (2001) Cytoplasmic recruitment of INI1 and PML on incoming HIV preintegration complexes: interference with early steps of viral replication. Molecular Cell 7:1245-1254.
95. Umland TC, Wei SQ, Craigie R & Davies DR (2000) Structural basis of DNA bridging by barrier-to-autointegration factor. Biochemistry 39:9130-9138.
96. Vandegraaff N, Kumar R, Hocking H, Burke TR, Mills J, Rhodes D, Burrell C & Li P (2001) Specific inhibition of human immunodeficiency virus type 1 (HIV-1) integration in cell culture: putative inhibitors of HIV-1 integrase Antimicrobial Agents and Chemotherapy 45:2510-2516.
97. van Gent DC, Groeneger AA & Plasterk RH (1992) Mutational analysis of the integrase protein of human immunodeficiency virus type 2. Proceedings of the National Academy of Sciences USA 89:9598-9602.
98. Vink C, Oude Groeneger AM & Plasterk RH (1993). Identification of the catalytic and DNA-binding region of the human immunodeficiency virus type I integrase protein. Nucleic Acids Research 21:1419-1425.
99. Wai JS, Egbertson MS, Payne LS, Fisher TE, Embrey MW, Tran LO, Melamed JY, Langford HM, Guare JP Jr, Zhuang L, Grey VE, Vacca JP, Holloway MK, Naylor-Olsen AM, Hazuda DJ, Felock PJ, Wolfe AL, Stillmock KA, Schleif WA, Gabryelski LJ & Young SD (2000) 4-Aryl-2,4-dioxobutanoic acid inhibitors of HIV-1 integrase and viral replication in cells. Journal of Medicinal Chemistry 43:4923-4926
100. Wang W, Cote J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL & Crabtree GR (1996) Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. The EMBO Journal 15:5370-5382.
101. Wang J-Y, Ling H, Yang W & Craigie R (2001) Structure of a twodomain fragment of HIV-1 integrase: implications for domain organization in the intact protein. The EMBO Journal 20:7333-7343.
102. Wu X, Liu H, Xiao H, Conway JA, Hehl E, Kalpana GV, Prasad V & Kappes JC (1999) Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. Journal of Virology 73:2126-2135.
103. Yi J, Arthur JW, Dunbrack RL Jr & Skalka AM (2000) An inhibitory monoclonal antibody binds at the turn of the helixturn-helix motif in the N-terminal domain of HIV-1 integrase. Journal of Biological Chemistry 275:38739-38748.
104. Yoder KE & Bushman FD (2000) Repair of gaps in retroviral DNA integration intermediates. Journal of Virology 74:11191-11200.
105. Yung E, Sorin M, Pal A, Craig E, Morozov A, Delattre O, Kappes J, Ott D & Kalpana GV (2001) Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1. Nature Medicine 7:920-926.
106. Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L & Charneau P (2000) HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101:173-185.
107. Zhao H, Neamati N, Sunder S, Hong H, Wang S, Milne GW, Pommier Y & Burke TR Jr (1997) Hydrazide-containing inhibitors of HIV-1 integrase. Journal of Medicinal Chemistry 40:937-941.
108. Zheng R, Jenkins TM & Craigie R (1996) Zinc folds the N-terminal domain ofHIV-1 integrase, promotes multimerization, and enhances catalytic activity. Proceedings of the National Academy of Sciences USA 93:13659-13664.