Citation: DING Qiong, ZHAO Lei, Hong GUO, Alan C. ZHENG. The Nucleocytoplasmic Transport of Viral Proteins* .VIROLOGICA SINICA, 2010, 25(2) : 79-85.  http://dx.doi.org/10.1007/s12250-010-3099-z

The Nucleocytoplasmic Transport of Viral Proteins*

cstr: 32224.14.s12250-010-3099-z
  • Corresponding author: Alan C. ZHENG, zhengcf@wh.iov.cn
  • Received Date: 04 September 2009
    Accepted Date: 28 December 2009
    Available online: 01 April 2010

    Fund Project: The Startup Fund of the Hundred Talents Program of the Chinese Academy of Science 20071010-141Open Research Fund Program of the State Key Laboratory of Virology of China 2007003Hubei Province Natural Science Foundation of Innovation Groups Project 2008CDA013Open Research Fund Program of the State Key Laboratory of Virology of China 2009007National Natural Science Foundation of China 30870120

  • Molecules can enter the nucleus by passive diffusion or active transport mechanisms, depending on their size. Small molecules up to size of 50-60 kDa or less than 10 nm in diameter can diffuse passively through the nuclear pore complex (NPC), while most proteins are transported by energy driven transport mechanisms. Active transport of viral proteins is mediated by nuclear localization signals (NLS), which were first identified in Simian Virus 40 large T antigen and had subsequently been identified in a large number of viral proteins. Usually they contain short stretches of lysine or arginine residues. These signals are recognized by the importin super-family (importin α and β) proteins that mediate the transport across the nuclear envelope through Ran-GTP. In contrast, only one class of the leucine-rich nuclear export signal (NES) on viral proteins is known at present. Chromosome region maintenance 1 (CRM1) protein mediates nuclear export of hundreds of viral proteins through the recognition of the leucine-rich NES.

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    1. Allen T D, Cronshaw J M, Bagley S, et al. 2000. The nuclear pore complex: mediator of translocation between nucleus and cytoplasm. J Cell Sci, 113 (Pt 10): 1651-1659.

    2. Bayliss R, Littlewood T, Stewart M. 2000. Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking. Cell, 102: 99-108.
        doi: 10.1016/S0092-8674(00)00014-3

    3. Boulo S, Akarsu H, Ruigrok R W, et al. 2007. Nuclear traffic of influenza virus proteins and ribonucleoprotein complexes. Virus Res, 124: 12-21.
        doi: 10.1016/j.virusres.2006.09.013

    4. Bremner K H, Seymour L W, Pouton C W. 2001. Harnessing nuclear localization pathways for transgene delivery. Curr Opin Mol Ther, 3: 170-177.

    5. Chen T, Brownawell A M, Macara I G. 2004. Nucleocytoplasmic shuttling of JAZ, a new cargo protein for exportin-5. Mol Cell Biol, 24: 6608-6619.
        doi: 10.1128/MCB.24.15.6608-6619.2004

    6. Conti E, Muller C W, Stewart M. 2006. Karyopherin flexibility in nucleocytoplasmic transport. Curr Opin Struct Biol, 16: 237-244.
        doi: 10.1016/j.sbi.2006.03.010

    7. Dingwall C, Robbins J, Dilworth S M, et al. 1988. The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen. J Cell Biol, 107: 841-849.
        doi: 10.1083/jcb.107.3.841

    8. Dong X, Biswas A, Suel K E, et al. 2009. Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature, 458: 1136-1141.
        doi: 10.1038/nature07975

    9. Eulalio A, Nunes-Correia I, Carvalho A L, et al. 2004. Two African swine fever virus proteins derived from a common precursor exhibit different nucleocytoplasmic transport activities. J Virol, 78: 9731-9739.
        doi: 10.1128/JVI.78.18.9731-9739.2004

    10. Fahrenkrog B, Aebi U. 2002. The vertebrate nuclear pore complex: from structure to function. Results Probl Cell Differ, 35: 25-48.
        doi: 10.1007/978-3-540-44603-3

    11. Fornerod M, Ohno M, Yoshida M, et al. 1997. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell, 90: 1051-1060.
        doi: 10.1016/S0092-8674(00)80371-2

    12. Fukuda M, Asano S, Nakamura T, et al. 1997. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature, 390: 308-311.
        doi: 10.1038/36894

    13. Guo H, Ding Q, Lin F, et al. 2009. Characterization of the Nuclear and Nucleolar Localization Signals of Bovine Herpesvirus-1 Infected Cell Protein 27. VirusRes, 145: 312-320.
        doi: 10.1016/j.virusres.2009.07.024

    14. Hodel M R, Corbett A H, Hodel A E. 2001. Dissection of a nuclear localization signal. J Biol Chem, 276: 1317-1325.
        doi: 10.1074/jbc.M008522200

    15. Kalab P, Weis K, Heald R. 2002. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science, 295: 2452-2456.
        doi: 10.1126/science.1068798

    16. Kalderon D, Richardson W D, Markham A F, et al. 1984. Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature, 311: 33-38.
        doi: 10.1038/311033a0

    17. Kosugi S, Hasebe M, Matsumura N, et al. 2009. Six classes of nuclear localization signals specific to different binding grooves of importin alpha. J Biol Chem, 284: 478-485.
        doi: 10.1074/jbc.M807017200

    18. Kudo N, Matsumori N, Taoka H, et al. 1999. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci USA, 96: 9112-9117.
        doi: 10.1073/pnas.96.16.9112

    19. la Cour T, Kiemer L, Molgaard A, et al. 2004. Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel, 17: 527-536.
        doi: 10.1093/protein/gzh062

    20. Lange A, Mills R E, Lange C J, et al. 2007. Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem, 282: 5101-5105.
        doi: 10.1074/jbc.R600026200

    21. Lee B J, Cansizoglu A E, Suel K E, et al. 2006. Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell, 126: 543-558.
        doi: 10.1016/j.cell.2006.05.049

    22. Lee C H, Chang S C, Wu C H, et al. 2001. A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly. J Biol Chem, 276: 8142-8148.
        doi: 10.1074/jbc.M004477200

    23. Lischka P, Rosorius O, Trommer E, et al. 2001. A novel transferable nuclear export signal mediates CRM1-independent nucleocytoplasmic shuttling of the human cytomegalovirus transactivator protein pUL69. EMBO J, 20: 7271-7283.
        doi: 10.1093/emboj/20.24.7271

    24. Michael W M, Choi M, Dreyfuss G. 1995. A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway. Cell, 83: 415-422.
        doi: 10.1016/0092-8674(95)90119-1

    25. Miyamoto Y, Imamoto N, Sekimoto T, et al. 1997. Differential modes of nuclear localization signal (NLS) recognition by three distinct classes of NLS receptors. J Biol Chem, 272: 26375-26381.
        doi: 10.1074/jbc.272.42.26375

    26. Nair R, Carter P, Rost B. 2003. NLSdb: database of nuclear localization signals. Nucleic Acids Res, 31: 397-399.
        doi: 10.1093/nar/gkg001

    27. Ossareh-Nazari B, Bachelerie F, Dargemont C. 1997. Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science, 278: 141-144.
        doi: 10.1126/science.278.5335.141

    28. Ossareh-Nazari B, Dargemont C. 1999. Domains of Crm1 involved in the formation of the Crm1, RanGTP, and leucine-rich nuclear export sequences trimeric complex. Exp Cell Res, 252: 236-241.
        doi: 10.1006/excr.1999.4599

    29. Peters R. 2006. Introduction to nucleocytoplasmic transport: molecules and mechanisms. Methods Mol Biol, 322: 235-258.
        doi: 10.1007/978-1-59745-000-3

    30. Quimby B B, Dasso M. 2003. The small GTPase Ran: interpreting the signs. Curr Opin Cell Biol, 15: 338-344.
        doi: 10.1016/S0955-0674(03)00046-2

    31. Roberts B L, Richardson W D, Smith A E. 1987. The effect of protein context on nuclear location signal function. Cell, 50: 465-475.
        doi: 10.1016/0092-8674(87)90500-9

    32. Rowland R R, Yoo D. 2003. Nucleolar-cytoplasmic shuttling of PRRSV nucleocapsid protein: a simple case of molecular mimicry or the complex regulation by nuclear import, nucleolar localization and nuclear export signal sequences. Virus Res, 95: 23-33.
        doi: 10.1016/S0168-1702(03)00161-8

    33. Siomi H, Dreyfuss G. 1995. A nuclear localization domain in the hnRNP A1 protein. J Cell Biol, 129: 551-560.
        doi: 10.1083/jcb.129.3.551

    34. Smith A E, Slepchenko B M, Schaff J C, et al. 2002. Systems analysis of Ran transport. Science, 295: 488-491.
        doi: 10.1126/science.1064732

    35. Suel K E, Chook Y M. 2009. Kap104p imports the PY-NLS-containing transcription factor Tfg2p into the nucleus. J Biol Chem, 284:15416-15424.
        doi: 10.1074/jbc.M809384200

    36. Zheng C, Brownlie R, Babiuk L A, et al. 2004. Characterization of nuclear localization and export signals of the major tegument protein VP8 of bovine herpesvirus-1. Virology, 324: 327-339.
        doi: 10.1016/j.virol.2004.03.042

    37. Zheng C, Brownlie R, Babiuk L A, et al. 2005.Characterization of the nuclear localization and nuclear export signals of bovine herpesvirus 1 VP22. J Virol, 79: 11864-11872.
        doi: 10.1128/JVI.79.18.11864-11872.2005

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    The Nucleocytoplasmic Transport of Viral Proteins*

      Corresponding author: Alan C. ZHENG, zhengcf@wh.iov.cn
    • State Key Laboratory, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    Fund Project:  The Startup Fund of the Hundred Talents Program of the Chinese Academy of Science 20071010-141Open Research Fund Program of the State Key Laboratory of Virology of China 2007003Hubei Province Natural Science Foundation of Innovation Groups Project 2008CDA013Open Research Fund Program of the State Key Laboratory of Virology of China 2009007National Natural Science Foundation of China 30870120

    Abstract: Molecules can enter the nucleus by passive diffusion or active transport mechanisms, depending on their size. Small molecules up to size of 50-60 kDa or less than 10 nm in diameter can diffuse passively through the nuclear pore complex (NPC), while most proteins are transported by energy driven transport mechanisms. Active transport of viral proteins is mediated by nuclear localization signals (NLS), which were first identified in Simian Virus 40 large T antigen and had subsequently been identified in a large number of viral proteins. Usually they contain short stretches of lysine or arginine residues. These signals are recognized by the importin super-family (importin α and β) proteins that mediate the transport across the nuclear envelope through Ran-GTP. In contrast, only one class of the leucine-rich nuclear export signal (NES) on viral proteins is known at present. Chromosome region maintenance 1 (CRM1) protein mediates nuclear export of hundreds of viral proteins through the recognition of the leucine-rich NES.