The HIV-1 passage from cytoplasm to nucleus: The process involving a complex exchange between the components of HIV-1 and cellular machinery to access nucleus and successful integration

International Journal of Biochemistry and Molecular Biology

Volumn 3, Issue 1, 2012, Pages 70-85

  Jayappa, Kallesh Danappa ^a   Ao, Zhujun ^a   Yao, Xiaojian ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Capsid; HIV 1; Importin; Integrase; Matrix; Nuclear import; Viral protein R

Indexed keywords

CAPSID PROTEIN; INTEGRASE; TRANSFER RNA; VIRUS DNA; VPR PROTEIN;

CELL COMPARTMENTALIZATION; CELL KINETICS; CELL NUCLEUS MATRIX; CELLULAR DISTRIBUTION; COMPLEX FORMATION; CYTOPLASM VESICLE; DISEASE COURSE; DNA INTEGRATION; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; INTERPHASE; INTRACELLULAR SIGNALING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; NONHUMAN; NUCLEAR IMPORT; NUCLEOCYTOPLASMIC TRANSPORT; REVIEW; VIRUS CELL INTERACTION; VIRUS ENTRY; VIRUS REPLICATION; VIRUS VIRULENCE;

HUMAN IMMUNODEFICIENCY VIRUS 1; MIRIDAE;

EID: 84859726305     PISSN: None     EISSN: 21524114     Source Type: Journal    
DOI: None     Document Type: Review

References (151)

1. Bour S, Geleziunas R, Wainberg MA: The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection. Microbiol Rev 1995, 59:63-93.
2. Doms RW, Peiper SC: Unwelcomed guests with master keys: how HIV uses chemokine receptors for cellular entry. Virology 1997, 235:179-190.
3. Fassati A, Goff SP: Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. J Virol 2001, 75:3626-3635.
4. Nermut MV, Fassati A: Structural analyses of purified human immunodeficiency virus type 1 intracellular reverse transcription complexes. J Virol 2003, 77:8196-8206.
5. Miller MD, Farnet CM, Bushman FD: Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition. J Virol 1997, 71:5382-5390.
6. Greene WC, Peterlin BM: Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapy. Nat Med 2002, 8:673-680.
7. Vodicka MA: Determinants for lentiviral infection of non-dividing cells. Somat Cell Mol Genet 2001, 26:35-49.
8. Bukrinsky MI, Haffar OK: HIV-1 nuclear import: matrix protein is back on center stage, this time together with Vpr. Mol Med 1998, 4:138-143.
9. Bukrinsky MI, Sharova N, Dempsey MP, Stan-wick TL, Bukrinskaya AG, Haggerty S, Steven-son M: Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci U S A 1992, 89:6580-6584.
10. de Noronha CM, Sherman MP, Lin HW, Cavrois MV, Moir RD, Goldman RD, Greene WC: Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr. Science 2001, 294:1105-1108.
11. Lewis P, Hensel M, Emerman M: Human immunodeficiency virus infection of cells arrested in the cell cycle. EMBO J 1992, 11:3053-3058.
12. Goldfarb DS, Corbett AH, Mason DA, Harreman MT, Adam SA: Importin alpha: a multipurpose nuclear-transport receptor. Trends Cell Biol 2004, 14:505-514.
13. Jayappa KD, Ao Z, Yang M, Wang J, Yao X: Identification of critical motifs within HIV-1 integrase required for importin alpha3 interaction and viral cDNA nuclear import. J Mol Biol 2011, 410:847-862.
14. Hearps AC, Jans DA: HIV-1 integrase is capable of targeting DNA to the nucleus via an importin alpha/beta-dependent mechanism. Biochem J 2006, 398:475-484.
15. Gallay P, Hope T, Chin D, Trono D: HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci U S A 1997, 94:9825-9830.
16. Depienne C, Mousnier A, Leh H, Le Rouzic E, Dormont D, Benichou S, Dargemont C: Characterization of the nuclear import pathway for HIV-1 integrase. J Biol Chem 2001, 276:18102-18107.
17. Ao Z, Huang G, Yao H, Xu Z, Labine M, Cochrane AW, Yao X: Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication. J Biol Chem 2007, 282:13456-13467.
18. Ao Z, Fowke KR, Cohen EA, Yao X: Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Retrovirology 2005, 2:62.
19. Heinzinger NK, Bukinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA, Gendelman HE, Ratner L, Stevenson M, Emerman M: The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci U S A 1994, 91:7311-7315.
20. Di Marzio P, Choe S, Ebright M, Knoblauch R, Landau NR: Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr. J Virol 1995, 69:7909-7916.
21. Jenkins Y, McEntee M, Weis K, Greene WC: Characterization of HIV-1 vpr nuclear import: analysis of signals and pathways. J Cell Biol 1998, 143:875-885.
22. Subbramanian RA, Yao XJ, Dilhuydy H, Rougeau N, Bergeron D, Robitaille Y, Cohen EA: Human immunodeficiency virus type 1 Vpr localization: nuclear transport of a viral protein modulated by a putative amphipathic helical structure and its relevance to biological activity. J Mol Biol 1998, 278:13-30.
23. Yao XJ, Subbramanian RA, Rougeau N, Boisvert F, Bergeron D, Cohen EA: Mutagenic analysis of human immunodeficiency virus type 1 Vpr: role of a predicted N-terminal al-pha-helical structure in Vpr nuclear localization and virion incorporation. J Virol 1995, 69:7032-7044.
24. Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M: A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 1993, 365:666-669.
25. Krishnan L, Matreyek KA, Oztop I, Lee K, Tipper CH, Li X, Dar MJ, Kewalramani VN, Engelman A: The requirement for cellular transportin 3 (TNPO3 or TRN-SR2) during infection maps to human immunodeficiency virus type 1 capsid and not integrase. J Virol 2010, 84:397-406.
26. Yamashita M, Emerman M: Capsid is a dominant determinant of retrovirus infectivity in nondividing cells. J Virol 2004, 78:5670-5678.
27. Dvorin JD, Bell P, Maul GG, Yamashita M, Emerman M, Malim MH: Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. J Virol 2002, 76:12087-12096.
28. Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau P: HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 2000, 101:173-185.
29. Ao Z, Yao X, Cohen EA: Assessment of the role of the central DNA flap in human immunodeficiency virus type 1 replication by using a single-cycle replication system. J Virol 2004, 78:3170-3177.
30. Arhel N, Munier S, Souque P, Mollier K, Charneau P: Nuclear import defect of human immunodeficiency virus type 1 DNA flap mutants is not dependent on the viral strain or target cell type. J Virol 2006, 80:10262-10269.
31. Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M: The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 1986, 233:215-219.
32. Weinberg JB, Matthews TJ, Cullen BR, Malim MH: Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes. J Exp Med 1991, 174:1477-1482.
33. Nicholson JK, Cross GD, Callaway CS, McDougal JS: In vitro infection of human monocytes with human T lymphotropic virus type III/ lymphadenopathy-associated virus (HTLV-III/ LAV). J Immunol 1986, 137:323-329.
34. Koyanagi Y, O'Brien WA, Zhao JQ, Golde DW, Gasson JC, Chen IS: Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Science 1988, 241:1673-1675.
35. Macatonia SE, Lau R, Patterson S, Pinching AJ, Knight SC: Dendritic cell infection, depletion and dysfunction in HIV-infected individuals. Immunology 1990, 71:38-45.
36. Patterson S, Knight SC: Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J Gen Virol 1987, 68 (Pt 4):1177-1181.
37. Roe T, Reynolds TC, Yu G, Brown PO: Integration of murine leukemia virus DNA depends on mitosis. EMBO J 1993, 12:2099-2108.
38. Lewis PF, Emerman M: Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol 1994, 68:510-516.
39. Springett GM, Moen RC, Anderson S, Blaese RM, Anderson WF: Infection efficiency of T lymphocytes with amphotropic retroviral vectors is cell cycle dependent. J Virol 1989, 63:3865-3869.
40. Miller DG, Adam MA, Miller AD: Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 1990, 10:4239-4242.
41. McDougal JS, Mawle A, Cort SP, Nicholson JK, Cross GD, Scheppler-Campbell JA, Hicks D, Sligh J: Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol 1985, 135:3151-3162.
42. Zagury D, Bernard J, Leonard R, Cheynier R, Feldman M, Sarin PS, Gallo RC: Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science 1986, 231:850-853.
43. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS: HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 1990, 61:213-222.
44. Bukrinsky MI, Sharova N, McDonald TL, Push-karskaya T, Tarpley WG, Stevenson M: Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection. Proc Natl Acad Sci U S A 1993, 90:6125-6129.
45. Gao WY, Cara A, Gallo RC, Lori F: Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication. Proc Natl Acad Sci U S A 1993, 90:8925-8928.
46. Cameron PU, Saleh S, Sallmann G, Solomon A, Wightman F, Evans VA, Boucher G, Haddad EK, Sekaly RP, Harman AN, et al: Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton. Proc Natl Acad Sci U S A 2010, 107:16934-16939.
47. Zack JA, Haislip AM, Krogstad P, Chen IS: Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol 1992, 66:1717-1725.
48. Ao Z, Danappa Jayappa K, Wang B, Zheng Y, Kung S, Rassart E, Depping R, Kohler M, Cohen EA, Yao X: Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1 nuclear import and replication. J Virol 2010, 84:8650-8663.
49. Katz RA, Greger JG, Boimel P, Skalka AM: Human immunodeficiency virus type 1 DNA nuclear import and integration are mitosis independent in cycling cells. J Virol 2003, 77:13412-13417.
50. Bouyac-Bertoia M, Dvorin JD, Fouchier RA, Jenkins Y, Meyer BE, Wu LI, Emerman M, Malim MH: HIV-1 infection requires a functional integrase NLS. Mol Cell 2001, 7:1025-1035.
51. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M: Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995, 373:123-126.
52. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, et al.: Viral dynamics in human immunodeficiency virus type 1 infection. Nature 1995, 373:117-122.
53. Ocwieja KE, Brady TL, Ronen K, Huegel A, Roth SL, Schaller T, James LC, Towers GJ, Young JA, Chanda SK, et al: HIV integration targeting: a pathway involving Transportin-3 and the nuclear pore protein RanBP2. PLoS Pathog 2011; 7:e1001313.
54. Konig R, Zhou Y, Elleder D, Diamond TL, Bonamy GM, Irelan JT, Chiang CY, Tu BP, De Jesus PD, Lilley CE, et al: Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 2008, 135:49-60.
55. Ho WZ, Cherukuri R, Douglas SD: The macro-phage and HIV-1. Immunol Ser 1994, 60:569-587.
56. Innocenti P, Ottmann M, Morand P, Leclercq P, Seigneurin JM: HIV-1 in blood monocytes: frequency of detection of proviral DNA using PCR and comparison with the total CD4 count. AIDS Res Hum Retroviruses 1992, 8:261-268.
57. Meltzer MS, Skillman DR, Gomatos PJ, Kalter DC, Gendelman HE: Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol 1990, 8:169-194.
58. Luby-Phelps K: Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. Int Rev Cytol 2000, 192:189-221.
59. Lukacs GL, Haggie P, Seksek O, Lechardeur D, Freedman N, Verkman AS: Size-dependent DNA mobility in cytoplasm and nucleus. J Biol Chem 2000, 275:1625-1629.
60. Dohner K, Wolfstein A, Prank U, Echeverri C, Dujardin D, Vallee R, Sodeik B: Function of dynein and dynactin in herpes simplex virus capsid transport. Mol Biol Cell 2002, 13:2795-2809.
61. Suomalainen M, Nakano MY, Keller S, Boucke K, Stidwill RP, Greber UF: Microtubule dependent plus and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J Cell Biol 1999, 144:657-672.
62. Ploubidou A, Moreau V, Ashman K, Reckmann I, Gonzalez C, Way M: Vaccinia virus infection disrupts microtubule organization and centro some function. EMBO J 2000, 19:3932-3944.
63. Ward BM: Visualization and characterization of the intracellular movement of vaccinia virus intracellular mature virions. J Virol 2005, 79:4755-4763.
64. Suikkanen S, Aaltonen T, Nevalainen M, Valilehto O, Lindholm L, Vuento M, Vihinen-Ranta M: Exploitation of microtubule cytoskeleton and dynein during parvoviral traffic toward the nucleus. J Virol 2003, 77:10270-10279.
65. McDonald D, Vodicka MA, Lucero G, Svitkina TM, Borisy GG, Emerman M, Hope TJ: Visuali-zation of the intracellular behavior of HIV in living cells. J Cell Biol 2002, 159:441-452.
66. Bukrinskaya A, Brichacek B, Mann A, Steven-son M: Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton. J Exp Med 1998, 188:2113-2125.
67. Yoder A, Guo J, Yu D, Cui Z, Zhang XE, Wu Y: Effects of microtubule modulators on HIV-1 infection of transformed and resting CD4 T cells. J Virol 2011, 85:3020-3024.
68. Vaughan JC, Brandenburg B, Hogle JM, Zhuang X: Rapid actin-dependent viral motility in live cells. Biophys J 2009, 97:1647-1656.
69. von Schwedler U, Kornbluth RS, Trono D: The nuclear localization signal of the matrix protein of human immunodeficiency virus type 1 allows the establishment of infection in macrophages and quiescent T lymphocytes. Proc Natl Acad Sci U S A 1994, 91:6992-6996.
70. Bukrinskaya AG, Ghorpade A, Heinzinger NK, Smithgall TE, Lewis RE, Stevenson M: Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA. Proc Natl Acad Sci U S A 1996, 93:367-371.
71. Burnette B, Yu G, Felsted RL: Phosphorylation of HIV-1 gag proteins by protein kinase C. J Biol Chem 1993, 268:8698-8703.
72. Cartier C, Deckert M, Grangeasse C, Trauger R, Jensen F, Bernard A, Cozzone A, Desgranges C, Boyer V: Association of ERK2 mitogen-activated protein kinase with human immunodeficiency virus particles. J Virol 1997, 71:4832-4837.
73. Jacque JM, Mann A, Enslen H, Sharova N, Brichacek B, Davis RJ, Stevenson M: Modulation of HIV-1 infectivity by MAPK, a virion associated kinase. EMBO J 1998, 17:2607-2618.
74. Gallay P, Swingler S, Aiken C, Trono D: HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell 1995, 80:379-388.
75. Gallay P, Swingler S, Song J, Bushman F, Trono D: HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 1995, 83:569-576.
76. Freed EO, Englund G, Maldarelli F, Martin MA: Phosphorylation of residue 131 of HIV-1 matrix is not required for macrophage infection. Cell 1997, 88:171-173; discussion 173-174.
77. Freed EO, Englund G, Martin MA: Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection. J Virol 1995, 69:3949-3954.
78. Mannioui A, Nelson E, Schiffer C, Felix N, Le Rouzic E, Benichou S, Gluckman JC, Canque B: Human immunodeficiency virus type 1 KK26-27 matrix mutants display impaired infectivity, circularization and integration but not nuclear import. Virology 2005, 339:21-30.
79. Haffar OK, Popov S, Dubrovsky L, Agostini I, Tang H, Pushkarsky T, Nadler SG, Bukrinsky M: Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex. J Mol Biol 2000, 299:359-368.
80. Reil H, Bukovsky AA, Gelderblom HR, Gottlinger HG: Efficient HIV-1 replication can occur in the absence of the viral matrix protein. EMBO J 1998, 17:2699-2708.
81. Cohen EA, Dehni G, Sodroski JG, Haseltine WA: Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol 1990, 64:3097-3099.
82. Lu YL, Spearman P, Ratner L: Human immuno-deficiency virus type 1 viral protein R localization in infected cells and virions. J Virol 1993, 67:6542-6550.
83. Morellet N, Bouaziz S, Petitjean P, Roques BP: NMR structure of the HIV-1 regulatory protein VPR. J Mol Biol 2003, 327:215-227.
84. Zhou Y, Lu Y, Ratner L: Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear localization and cell cycle arrest. Virology 1998, 242:414-424.
85. He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR: Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 1995, 69:6705-6711.
86. Karni O, Friedler A, Zakai N, Gilon C, Loyter A: A peptide derived from the N-terminal region of HIV-1 Vpr promotes nuclear import in permeabilized cells: elucidation of the NLS region of the Vpr. FEBS Lett 1998, 429:421-425.
87. Gallay P, Stitt V, Mundy C, Oettinger M, Trono D: Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import. J Virol 1996, 70:1027-1032.
88. Kamata M, Nitahara-Kasahara Y, Miyamoto Y, Yoneda Y, Aida Y: Importin-alpha promotes passage through the nuclear pore complex of human immunodeficiency virus type 1 Vpr. J Virol 2005, 79:3557-3564.
89. Nitahara-Kasahara Y, Kamata M, Yamamoto T, Zhang X, Miyamoto Y, Muneta K, Iijima S, Yoneda Y, Tsunetsugu-Yokota Y, Aida Y: Novel nuclear import of Vpr promoted by importin alpha is crucial for human immunodeficiency virus type 1 replication in macrophages. J Virol 2007, 81:5284-5293.
90. Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G, Bukrinsky M: Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J 1998, 17:909-917.
91. Jacquot G, Le Rouzic E, David A, Mazzolini J, Bouchet J, Bouaziz S, Niedergang F, Pancino G, Benichou S: Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Retrovirology 2007, 4:84.
92. Varadarajan P, Mahalingam S, Liu P, Ng SB, Gandotra S, Dorairajoo DS, Balasundaram D: 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 2005, 16:1823-1838.
93. Le Rouzic E, Mousnier A, Rustum C, Stutz F, Hallberg E, Dargemont C, Benichou S: Docking of HIV-1 Vpr to the nuclear envelope is mediated by the interaction with the nucleoporin hCG1. J Biol Chem 2002, 277:45091-45098.
94. Fouchier RA, Meyer BE, Simon JH, Fischer U, Albright AV, Gonzalez-Scarano F, Malim MH: Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex. J Virol 1998, 72:6004-6013.
95. Vodicka MA, Koepp DM, Silver PA, Emerman M: HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 1998, 12:175-185.
96. Connor RI, Chen BK, Choe S, Landau NR: Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 1995, 206:935-944.
97. Depienne C, Roques P, Creminon C, Fritsch L, Casseron R, Dormont D, Dargemont C, Benichou S: Cellular distribution and karyo-philic properties of matrix, integrase, and Vpr proteins from the human and simian immunodeficiency viruses. Exp Cell Res 2000, 260:387-395.
98. Ikeda T, Nishitsuji H, Zhou X, Nara N, Ohashi T, Kannagi M, Masuda T: Evaluation of the functional involvement of human immunodeficiency virus type 1 integrase in nuclear import of viral cDNA during acute infection. J Virol 2004, 78:11563-11573.
99. Zheng R, Jenkins TM, Craigie R: Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity. Proc Natl Acad Sci U S A 1996, 93:13659-13664.
100. Tsurutani N, Kubo M, Maeda Y, Ohashi T, Ya mamoto N, Kannagi M, Masuda T: 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 2000, 74:4795-4806.
101. Cannon PM, Byles ED, Kingsman SM, Kingsman AJ: Conserved sequences in the carboxyl terminus of integrase that are essential for human immunodeficiency virus type 1 replication. J Virol 1996, 70:651-657.
102. Pluymers W, Cherepanov P, Schols D, De Clercq E, Debyser Z: Nuclear localization of human immunodeficiency virus type 1 integrase expressed as a fusion protein with green fluorescent protein. Virology 1999, 258:327-332.
103. Petit C, Schwartz O, Mammano F: The karyophilic properties of human immunodeficiency virus type 1 integrase are not required for nuclear import of proviral DNA. J Virol 2000, 74:7119-7126.
104. Kukolj G, Jones KS, Skalka AM: Subcellular localization of avian sarcoma virus and human immunodeficiency virus type 1 integrases. J Virol 1997, 71:843-847.
105. Devroe E, Engelman A, Silver PA: Intracellular transport of human immunodeficiency virus type 1 integrase. J Cell Sci 2003, 116:4401-4408.
106. Lu R, Limon A, Devroe E, Silver PA, Cherepanov P, Engelman A: 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. J Virol 2004, 78:12735-12746.
107. Limon A, Devroe E, Lu R, Ghory HZ, Silver PA, Engelman A: 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 2002, 76:10598-10607.
108. Christ F, Thys W, De Rijck J, Gijsbers R, Al-banese A, Arosio D, Emiliani S, Rain JC, Benarous R, Cereseto A, Debyser Z: Transportin-SR2 imports HIV into the nucleus. Curr Biol 2008, 18:1192-1202.
109. Fassati A, Gorlich D, Harrison I, Zaytseva L, Mingot JM: Nuclear import of HIV-1 intracellular reverse transcription complexes is mediated by importin 7. EMBO J 2003, 22:3675-3685.
110. Zielske SP, Stevenson M: Importin 7 may be dispensable for human immunodeficiency virus type 1 and simian immunodeficiency virus infection of primary macrophages. J Virol 2005, 79:11541-11546.
111. Zaitseva L, Cherepanov P, Leyens L, Wilson SJ, Rasaiyaah J, Fassati A: HIV-1 exploits importin 7 to maximize nuclear import of its DNA genome. Retrovirology 2009, 6:11.
112. Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, Lieberman J, Elledge SJ: Identification of host proteins required for HIV infection through a functional genomic screen. Science 2008, 319:921-926.
113. Kataoka N, Bachorik JL, Dreyfuss G: Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol 1999, 145:1145-1152.
114. Lai MC, Lin RI, Huang SY, Tsai CW, Tarn WY: A human importin-beta family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J Biol Chem 2000, 275:7950-7957.
115. Armon-Omer A, Levin A, Hayouka Z, Butz K, Hoppe-Seyler F, Loya S, Hizi A, Friedler A, Loyter A: Correlation between shiftide activity and HIV-1 integrase inhibition by a peptide selected from a combinatorial library. J Mol Biol 2008, 376:971-982.
116. Levin A, Hayouka Z, Friedler A, Loyter A: Transportin 3 and importin alpha are required for effective nuclear import of HIV-1 integrase in virus-infected cells. Nucleus 2010, 1:422-431.
117. Logue EC, Taylor KT, Goff PH, Landau NR: The cargo-binding domain of transportin 3 is required for lentivirus nuclear import. J Virol 2011, 85:12950-12961.
118. Kohler M, Speck C, Christiansen M, Bischoff FR, Prehn S, Haller H, Gorlich D, Hartmann E: Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import. Mol Cell Biol 1999, 19:7782-7791.
119. Lange A, Mills RE, Lange CJ, Stewart M, Devine SE, Corbett AH: Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem 2007, 282:5101-5105.
120. Kohler M, Fiebeler A, Hartwig M, Thiel S, Prehn S, Kettritz R, Luft FC, Hartmann E: Differential expression of classical nuclear transport factors during cellular proliferation and differentiation. Cell Physiol Biochem 2002, 12:335-344.
121. Yasuhara N, Shibazaki N, Tanaka S, Nagai M, Kamikawa Y, Oe S, Asally M, Kamachi Y, Kon-doh H, Yoneda Y: Triggering neural differentiation of ES cells by subtype switching of im portin-alpha. Nat Cell Biol 2007, 9:72-79.
122. Woodward CL, Prakobwanakit S, Mosessian S, Chow SA: Integrase interacts with nucleoporin NUP153 to mediate the nuclear import of human immunodeficiency virus type 1. J Virol 2009, 83:6522-6533.
123. Matreyek KA, Engelman A: The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid. J Virol 2011, 85:7818-7827.
124. Lee K, Ambrose Z, Martin TD, Oztop I, Mulky A, Julias JG, Vandegraaff N, Baumann JG, Wang R, Yuen W, et al: Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 2010, 7:221-233.
125. Ebina H, Aoki J, Hatta S, Yoshida T, Koyanagi Y: Role of Nup98 in nuclear entry of human immunodeficiency virus type 1 cDNA. Microbes Infect 2004, 6:715-724.
126. Fassati A, Goff SP: Characterization of intracellular reverse transcription complexes of Molo-ney murine leukemia virus. J Virol 1999, 73:8919-8925.
127. Dismuke DJ, Aiken C: Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. J Virol 2006, 80:3712-3720.
128. Bowerman B, Brown PO, Bishop JM, Varmus HE: A nucleoprotein complex mediates the integration of retroviral DNA. Genes Dev 1989, 3:469-478.
129. Charneau P, Clavel F: A single-stranded gap in human immunodeficiency virus unintegrated linear DNA defined by a central copy of the polypurine tract. J Virol 1991, 65:2415-2421.
130. Riviere L, Darlix JL, Cimarelli A: Analysis of the viral elements required in the nuclear import of HIV-1 DNA. J Virol 2010; 84:729-739.
131. Charneau P, Alizon M, Clavel F: A second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication. J Virol 1992, 66:2814-2820.
132. Iglesias C, Ringeard M, Di Nunzio F, Fernandez J, Gaudin R, Souque P, Charneau P, Arhel N: Residual HIV-1 DNA Flap-independent nuclear import of cPPT/CTS double mutant viruses does not support spreading infection. Retrovirology 2011, 8:92.
133. Marsden MD, Zack JA: Human immunodeficiency virus bearing a disrupted central DNA flap is pathogenic in vivo. J Virol 2007, 81:6146-6150.
134. De Rijck J, Debyser Z: The central DNA flap of the human immunodeficiency virus type 1 is important for viral replication. Biochem Bio-phys Res Commun 2006, 349:1100-1110.
135. Arhel NJ, Souquere-Besse S, Munier S, Souque P, Guadagnini S, Rutherford S, Prevost MC, Allen TD, Charneau P: HIV-1 DNA Flap formation promotes uncoating of the preintegration complex at the nuclear pore. EMBO J 2007, 26:3025-3037.
136. Follenzi A, Ailles LE, Bakovic S, Geuna M, Naldini L: Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet 2000, 25:217-222.
137. Zennou V, Serguera C, Sarkis C, Colin P, Perret E, Mallet J, Charneau P: The HIV-1 DNA flap stimulates HIV vector-mediated cell transduction in the brain. Nat Biotechnol 2001, 19:446-450.
138. Manganini M, Serafini M, Bambacioni F, Casati C, Erba E, Follenzi A, Naldini L, Bernasconi S, Gaipa G, Rambaldi A, et al: A human immunodeficiency virus type 1 pol genederived sequence (cPPT/CTS) increases the efficiency of transduction of human nondividing monocytes and T lymphocytes by lentiviral vectors. Hum Gene Ther 2002, 13:1793-1807.
139. Van Maele B, De Rijck J, De Clercq E, Debyser Z: Impact of the central polypurine tract on the kinetics of human immunodeficiency virus type 1 vector transduction. J Virol 2003, 77:4685-4694.
140. Zaitseva L, Myers R, Fassati A: tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes. PLoS Biol 2006, 4:e332.
141. Varmus HE, Padgett T, Heasley S, Simon G, Bishop JM: Cellular functions are required for the synthesis and integration of avian sarcoma virus-specific DNA. Cell 1977, 11:307-319.
142. Humphries EH, Glover C, Reichmann ME: Rous sarcoma virus infection of synchronized cells establishes provirus integration during Sphase DNA synthesis prior to cellular division. Proc Natl Acad Sci U S A 1981, 78:2601-2605.
143. Casolari JM, Brown CR, Komili S, West J, Hieronymus H, Silver PA: Genome-wide localization of the nuclear transport machinery couples transcriptional status and nuclear organization. Cell 2004, 117:427-439.
144. Schmid M, Arib G, Laemmli C, Nishikawa J, Durussel T, Laemmli UK: Nup-PI: the nucleo-pore-promoter interaction of genes in yeast. Mol Cell 2006, 21:379-391.
145. Kalverda B, Pickersgill H, Shloma VV, Fornerod M: Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm. Cell 2010, 140:360-371.
146. Daigle N, Beaudouin J, Hartnell L, Imreh G, Hallberg E, Lippincott-Schwartz J, Ellenberg J: Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells. J Cell Biol 2001, 154:71-84.
147. Rabut G, Doye V, Ellenberg J: Mapping the dynamic organization of the nuclear pore complex inside single living cells. Nat Cell Biol 2004, 6:1114-1121.
148. Lindsay ME, Plafker K, Smith AE, Clurman BE, Macara IG: Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:betamediated nuclear protein import. Cell 2002, 110:349-360.
149. Griffis ER, Craige B, Dimaano C, Ullman KS, Powers MA: Distinct functional domains within nucleoporins Nup153 and Nup98 mediate transcription-dependent mobility. Mol Biol Cell 2004, 15:1991-2002.
150. Griffis ER, Altan N, Lippincott-Schwartz J, Powers MA: Nup98 is a mobile nucleoporin with transcription-dependent dynamics. Mol Biol Cell 2002, 13:1282-1297.
151. Ao Z, Danappa Jayappa K, Wang B, Zheng Y, Wang X, Peng J, Yao X: Contribution of host nucleoporin 62 in HIV-1 integrase chromatin association and viral DNA integration. J Biol Chem 2012.