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Nuclear Import and Export of Mammalian Viruses

  • Michael Bukrinsky
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

Viruses are intracellular parasites that commandeer cellular processes, such as RNA processing or protein synthesis, to perform virus-specific functions. For this purpose, many viral proteins shuttle between the nuclear and cytoplasmic compartments, even when the viral genome is replicated in the cytoplasm. This shutding process is usually regulated by classical nuclear import and export signals (NLSs and NESs, respeaively), which are also found in many cellular proteins and are described elsewhere in this book. In this Chapter, we will focus on viruses that replicate in the nucleus, and in particular on the mechanisms by which they transport their genomes into and out of the nucleus.

Keywords

Human Immunodeficiency Virus Type Nuclear Export Nuclear Import Nuclear Export Signal Constitutive Transport Element 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Agostini I, Popov S, Li J et al. Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral pre-integration complex. Exp Cell Res 2000; 259:398–403.PubMedCrossRefGoogle Scholar
  2. 2.
    Baines JD, Jacob RJ, Simmerman L et al. The herpes simplex virus 1 UL11 proteins are associated with cytoplasmic and nuclear membranes and with nuclear bodies of infected cells. J Virol 1995; 69:825–833.PubMedGoogle Scholar
  3. 3.
    Baines JD, Roizman B. The UL11 gene of herpes simplex virus 1 encodes a function that facilitates nucleocapsid envelopment and egress from cells. J Virol. 1992; 66:5168–5174.PubMedGoogle Scholar
  4. 4.
    Baines JD, Ward PL, Campadelli-Fiume G et al. The UL20 gene of herpes simplex virus 1 encodes a function necessary for viral egress. J Virol. 1991; 65:6414–6424.PubMedGoogle Scholar
  5. 5.
    Bear J, Tan W, Zolotukhi AS et al. Identification of novel import and export signals of human TAP, the protein that binds to the constitutive transport element of the type D retrovirus mRNAs. Mol Cell Biol 1999; 19:6306–6317.PubMedGoogle Scholar
  6. 6.
    Bevec D, Jaksche H, Oft M et al. Inhibition of HIV-1 replication in lymphocytes by mutants of the Rev cofactor eIF-5A. Science 1996; 271:1858–1860.PubMedCrossRefGoogle Scholar
  7. 7.
    Braun IC, Rohrbach E, Schmitt C et al. TAP binds to the constitutive transport element (CTE) through a novel RNA-binding motif that is sufficient to promote CTE-dependent RNA export from the nucleus. EMBO J 1999; 18:1953–1965.PubMedCrossRefGoogle Scholar
  8. 8.
    Bray M, Prasad S, Dubay JW et al. A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci USA 1994; 91:1256–1260.PubMedCrossRefGoogle Scholar
  9. 9.
    Bui M, Wills EG, Helenius A et al. Role of the influenza virus Ml protein in nuclear export of viral ribonucleoproteins. J Virol 2000; 74:1781–1786.PubMedCrossRefGoogle Scholar
  10. 10.
    Bukrinskaya A, Brichacek B, Mann A et al. Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton. J Exp Med 1998; 188:2113–2125.PubMedCrossRefGoogle Scholar
  11. 11.
    Bukrinsky MI, Haggerty S, Dempsey MP et al. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 1993; 365:666–669.PubMedCrossRefGoogle Scholar
  12. 12.
    Bukrinsky MI, Sharova N, McDonald TL et al. 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 USA 1993; 90:6125–6129.PubMedCrossRefGoogle Scholar
  13. 13.
    Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Re. Cell Dev Biol 1997; 13:83–117.CrossRefGoogle Scholar
  14. 14.
    Dubrovsky L, Ulrich P, Nuovo GJ et al. Nuclear localization signal of HIV-1 as a novel target for therapeutic intervention. Mol Med 1995; 1:217–230.PubMedGoogle Scholar
  15. 15.
    Dupont S, Sharova N, DeHoratius C et al. A novel nuclear export activity in HIV-1 matrix protein required for viral replication. Nature 1999; 402:681–685.PubMedCrossRefGoogle Scholar
  16. 16.
    Dworetzky SI, Lanford RE, Feldherr CM. The effects of variations in the number and sequence of targeting signals on nuclear uptake. J Cell Biol 1998; 107:1279–1287.CrossRefGoogle Scholar
  17. 17.
    Elfgang C, Rosorius O, Hofer L et al. Evidence for specific nucleocytoplasmic transport pathways used by leucine-rich nuclear export signals. Proc Natl Acad Sci USA 1999; 96:6229–6234.PubMedCrossRefGoogle Scholar
  18. 18.
    Elton D, Simpson-Holley M, Archer K et al. Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway. J Virol 2001; 75:408–419.PubMedCrossRefGoogle Scholar
  19. 19.
    Emerman M, Bukrinsky M, Stevenson M. HIV-1 infection of non-dividing cells. Nature 1994; 369:107–108.CrossRefGoogle Scholar
  20. 20.
    Farnet CM, Haseltine WA. Determination of viral proteins present in the human immunodeficiency virus type 1 preintegration complex. J Virol 1991; 65:1910–1915.PubMedGoogle Scholar
  21. 21.
    Fassati A, Goff SP. Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. J Virol 2001; 75:3626–3635.PubMedCrossRefGoogle Scholar
  22. 22.
    Follenzi A, Ailles LE, Bakovic S et al. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet 2000; 25:217–222.PubMedCrossRefGoogle Scholar
  23. 23.
    Fornerod M, Ohno M, Yoshida M et al. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 1997; 90:1051–1060.PubMedCrossRefGoogle Scholar
  24. 24.
    Fornerod M, van Deursen J, van Baal S et al. The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. EMBO J 1997; 16:807–816.PubMedCrossRefGoogle Scholar
  25. 25.
    Fouchier RA, Meyer BE, Simon JH et al. Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex. J Virol 1998; 72:6004–6013.PubMedGoogle Scholar
  26. 26.
    Fouchier RA, Meyer BE, Simon JH et al. HIV-1 infection of non-dividing cells: Evidence that the amino-terminal basic region of the viral matrix protein is important for Gag processing but not for post-entry nuclear import. EMBO J 1997; 16:4531–4539.PubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedGoogle Scholar
  28. 28.
    Fritz CC, Green MR. HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAs. Curr Biol 1996; 6:848–854.PubMedCrossRefGoogle Scholar
  29. 29.
    Fritz CC, Zapp ML, Green MR. A human nucleoporin-like protein that specifically interacts with HIV Rev Nature 1995; 376:530–533.Google Scholar
  30. 30.
    Gallay P, Hope T, Chin D et al. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci USA 1997; 94:9825–9830.PubMedCrossRefGoogle Scholar
  31. 31.
    Gallay P, Stitt V, Mundy C et al. Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import. J Virol 1996; 70:1027–1032.PubMedGoogle Scholar
  32. 32.
    Gallay P, Swingler S, Song J et al. HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 1995; 83:569–576.PubMedCrossRefGoogle Scholar
  33. 33.
    Glushakova S, Dubrovsky L, Grivel JC et al. Small molecule inhibitor of HIV-1 nuclear import suppresses HIV-1 replication in human lymphoid tissue ex vivo: A potential addition to current anti-HIV drug repertoire. Antiviral Res 2000; 47:89–95.PubMedCrossRefGoogle Scholar
  34. 34.
    Gruter P, Tabernero C, von Kobbe C et al. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell 1998; 1:649–659.PubMedCrossRefGoogle Scholar
  35. 35.
    Guddat U, Bakken AH, Pieler T. Protein-mediated nuclear export of RNA: 5S rRNA containing small RNPs in xenopus oocytes. Cell 1998; 60:619–628.CrossRefGoogle Scholar
  36. 36.
    Haffar OK, Popov S, Dubrovsky L et al. 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.PubMedCrossRefGoogle Scholar
  37. 37.
    Haffar OK, Smithgall MD, Popov S et al. CNI-H0294, a nuclear importation inhibitor of the human immunodeficiency virus type 1 genome, abrogates virus replication in infected activated peripheral blood mononuclear cells. Antimicrob Agents Chemother 1998; 42:1133–1138.PubMedGoogle Scholar
  38. 38.
    Harley CA, Dasgupta A, Wilson DW. Characterization of herpes simplex virus-containing organelles by subcellular fractionation: Role for organelle acidification in assembly of infectious particles. J Virol 2001; 75:1236–1251.PubMedCrossRefGoogle Scholar
  39. 39.
    Heinzinger NK, Bukrinsky MI, Haggerty SA et al. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci USA 1994; 91:7311–7315.PubMedCrossRefGoogle Scholar
  40. 40.
    Hernandez LD, Hoffman LR, Wolfsberg TG et al. Virus-cell and cell-cell fusion. Annu Rev Cell Dev Biol 1996; 12:627–661.PubMedCrossRefGoogle Scholar
  41. 41.
    Herold A, Truant R, Wiegand H et al. Determination of the functional domain organization of the importin alpha nuclear import factor. J Cell Biol 1998; 143:309–318.PubMedCrossRefGoogle Scholar
  42. 42.
    Hofmann W, Reichart B, Ewald A et al. Cofactor requirements for nuclear export of Rev response element (RRE)-and constitutive transport element (CTE)-containing retroviral RNAs. An unexpected role for actin. J Cell Biol 2001; 152:895–910.PubMedCrossRefGoogle Scholar
  43. 43.
    Imamoto N, Matsuoka Y, Kurihara T et al. Antibodies against 70-kD heat shock cognate protein inhibit mediated nuclear import of karyophilic proteins. J Cell Biol 1992; 119:1047–1061.PubMedCrossRefGoogle Scholar
  44. 44.
    Jenkins Y, McEntee M, Weis K et al. Characterization of HIV-1 vpr nuclear import: Analysis of signals and pathways. J Cell Biol 1998; 143:875–885.PubMedCrossRefGoogle Scholar
  45. 45.
    Jeoung DI, Chen S, Windsor J et al. Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells. Genes Dev 1991; 5:2235–2244.PubMedGoogle Scholar
  46. 46.
    Kang Y, Cullen BR. The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. Genes Dev 1999; 13:1126–1139.PubMedGoogle Scholar
  47. 47.
    Martin K, Helenius A. Nuclear transport of influenza virus ribonucleoproteins: The viral matrix protein (M1) promotes export and inhibits import. Cell 1991; 67:117–130.PubMedCrossRefGoogle Scholar
  48. 48.
    Meyer BE, Meinkoth JL, Malim MH. Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev proteins: Identification of a family of transfer able nuclear export signals. J Virol 1996; 70:2350–2359.PubMedGoogle Scholar
  49. 49.
    Miller MD, Farnet CM, Bushman FD. Human immunodeficiency virus type 1 preintegration complexes: Studies of organization and composition. J Virol 1997; 71:5382–5390.PubMedGoogle Scholar
  50. 50.
    Nadler SG, Tritschler D, Haffar OK et al. Differential expression and sequence-specific interaction of karyopherin alpha with nuclear localization sequences. J Biol Chem 1997; 272:4310–4315.PubMedCrossRefGoogle Scholar
  51. 51.
    Nemerow GR. Cell receptors involved in adenovirus entry. Virology 2000; 274:1–4.PubMedCrossRefGoogle Scholar
  52. 52.
    Newcomb W, Brown JC. Induced extrusion of DNA from the capsid of herpes simplex virus type 1. J Virol 1994; 68:433–440.PubMedGoogle Scholar
  53. 53.
    O’Neill RE, Jaskunas R, Blobel G et al. Nuclear import of influenza virus RNA can be mediated by viral nucleoprotein and transport factors required for protein import. J Biol Chem 155;270:22701–22704.Google Scholar
  54. 54.
    O’Neill RE, Talon J, Palese P. The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J 1998; 17:288–296.PubMedCrossRefGoogle Scholar
  55. 55.
    Okuno Y, Imamoto N, Yoneda Y. 70-kDa heat-shock cognate protein colocalizes with karyophilic proteins into the nucleus during their transport in vitro. Exp Cell Res 1993; 206:134–142.PubMedCrossRefGoogle Scholar
  56. 56.
    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.PubMedCrossRefGoogle Scholar
  57. 57.
    Pollard VW, Malim MH. The HIV-1 Rev protein. Annu Rev Microbiol 1998; 52:491–532.PubMedCrossRefGoogle Scholar
  58. 58.
    Popov S, Dubrovsky L, Lee MA et al. Critical role of reverse transcriptase in the inhibitory mechanism of CNI-H0294 on HIV-1 nuclear translocation. Proc Natl Acad Sci USA 1996; 93:11859–11864.PubMedCrossRefGoogle Scholar
  59. 59.
    Popov S, Rexach M, Ratner L et al. Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex. J Biol Chem 1998; 273:13347–13352.PubMedCrossRefGoogle Scholar
  60. 60.
    Popov S, Rexach M, Zybarth G et al. Viral protein R regulates nuclear import of the HIV-1 preintegration complex. EMBO J 1998; 17:909–917.PubMedCrossRefGoogle Scholar
  61. 61.
    Roe T, Reynolds TC, Yu G et al. Integration of murine leukemia virus DNA depends on mitosis. EMBO J 1993; 12:2099–2108.PubMedGoogle Scholar
  62. 62.
    Roizman B, Sears AY. Herpes simplex viruses and their replication. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. Philadelphia: Lippincott-Raven, 1996:2231–2295.Google Scholar
  63. 63.
    Rosorius O, Reichart B, Kratzer F et al. Nuclear pore localization and nucleocytoplasmic transport of eIF-5A: Evidence for direct interaction with the export receptor CRM1. J Cell Sci 1999; 112:2369–2380.PubMedGoogle Scholar
  64. 64.
    Roth J, Dobbelstein M. Export of hepatitis B virus RNA on a Rev-like pathway: Inhibition by the regenerating liver inhibitory factor IkappaB alpha. J Virol 1997; 71:8933–8939.PubMedGoogle Scholar
  65. 65.
    Ruhl M, Himmelspach M, Bahr GM et al. Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation. J Cell Biol 1993; 123:1309–1320.PubMedCrossRefGoogle Scholar
  66. 66.
    Schatz O, Oft M, Dascher C et al. Interaction of the HIV-1 rev cofactor eukaryotic initiation factor 5A with ribosomal protein L5. Proc Natl Acad Sci USA 1998; 95:1607–1612.PubMedCrossRefGoogle Scholar
  67. 67.
    Sherman MP, de Noronha CM, Heusch MI et al. Nucleocytoplasmic shuttling by human immunodeficiency virus type 1 Vpr. J Virol 2001; 75:1522–1532.PubMedCrossRefGoogle Scholar
  68. 68.
    Shi Y, Thomas JO. The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate. Mol Cell Biol 1992; 12:2186–2192.PubMedGoogle Scholar
  69. 69.
    Skepper JN, Whiteley A, Browne H et al. Herpes simplex virus nucleocapsids mature to progeny virions by an envelopment → deenvelopment → reenvelopment pathway. J Virol 2001; 75:5697–5702.PubMedCrossRefGoogle Scholar
  70. 70.
    Sodeik B, Ebersold MW, Helenius A. Microtubule-mediated transport of incoming herpes simplex virus 1 capsids to the nucleus. J Cell Biol 1997; 136:1007–1021.PubMedCrossRefGoogle Scholar
  71. 71.
    Steitz JA, Berg C, Hendrick JP et al. A 5S rRNA/L5 complex is a precursor to ribosome assembly in mammalian cells. J Cell Biol 1988; 106:545–556.PubMedCrossRefGoogle Scholar
  72. 72.
    Suomalainen M, Nakano MY, Boucke K et al. Adenovirus-activated PKA and p38/MAPK path ways boost microtubule-mediated nuclear targeting of virus. EMBO J 2001; 20:1310–1319.PubMedCrossRefGoogle Scholar
  73. 73.
    Suomalainen M, Nakano MY, Keller S et al. Microtubule-dependent plus-and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J Cell Biol 1999; 144:657–672.PubMedCrossRefGoogle Scholar
  74. 74.
    Telesnitsky A, Goff SP. Reverse transcriptase and the generation of retroviral DNA. In: Coffin JM, Highes SH, Varmus HE, eds. Retroviruses. Cold Spring Harbor: Cold Spring Harbor Press, 1997:121–160.Google Scholar
  75. 75.
    Vodicka MA, Koepp DM, Silver PA et al. HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 1998; 12:175–185.PubMedGoogle Scholar
  76. 76.
    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 USA 1994; 91:6992–6996.CrossRefGoogle Scholar
  77. 77.
    Weis K, Ryder U, Lamond Al. The conserved amino-terminal domain of hSRPl alpha is essential for nuclear protein import. EMBO J 1996; 15:1818–1825.PubMedGoogle Scholar
  78. 78.
    Wen W, Meinkoth JL, Tsien RY et al. Identification of a signal for rapid export of proteins from the nucleus. Cell 1995; 82:463–473.PubMedCrossRefGoogle Scholar
  79. 79.
    Whittaker GR, Helenius A. Nuclear import and export of viruses and virus genomes. Virology 1998; 246:1–23.PubMedCrossRefGoogle Scholar
  80. 80.
    Whittaker GR, Kann M, Helenius A. Viral entry into the nucleus. Annu Rev Cell Dev Biol 2000; 16:627–651.PubMedCrossRefGoogle Scholar
  81. 81.
    Yang J, DeFranco DB. Differential roles of heat shock protein 70 in the in vitro nuclear import of glucocorticoid receptor and simian virus 40 large tumor antigen. Mol Cell Biol 1994; 14:5088–5098.PubMedGoogle Scholar
  82. 82.
    Yoneda Y. Nucleocytoplasmic protein traffic and its significance to cell function. Genes Cells 2000; 5:777–787.PubMedCrossRefGoogle Scholar
  83. 83.
    Zennou V, Petit C, Guetard D et al. HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 2000; 101:173–185.PubMedCrossRefGoogle Scholar
  84. 84.
    Zhirnov OP, Klenk HD. Histones as a target for influenza virus matrix protein Ml. Virology 1997; 235:302–310.PubMedCrossRefGoogle Scholar
  85. 85.
    Zhu Z, Gershon MD, Hao Y et al. Envelopment of varicella-zoster virus: targeting of viral glycoproteins to the trans-Golgi network. J Virol 1995; 69:7951–7959.PubMedGoogle Scholar
  86. 86.
    Zufferey R, Nagy D, Mandel RJ et al. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 1997; 15:871–875.PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  • Michael Bukrinsky
    • 1
  1. 1.Department of Microbiology and Tropical MedicineGeorge Washington UniversityWashington, DCUSA

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