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The regulation of disassembly of alphavirus cores

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Abstract

Alphaviruses are used as model viruses for structure determination and for analysis of virus entry. They are used also as vectors for protein expression and gene therapy. Virus particles are assembled by budding, using preformed cores and a modified cellular membrane. During entry, alphaviruses release the viral core into the cytoplasm. Cores are disassembled during virus entry and accumulate in the cytoplasm during virus multiplication. The regulation of core disassembly is the subject of this review. A working model compatible with all experimental data is formulated. This model comprises the following steps: (1) The incoming core is present in the cytoplasm in a metastable state, primed for disassembly. A core structure containing the so-called linker region of the core protein in an exposed position susceptible to proteolytic cleavage on the core surface might represent the primed state. (2) The primed core allows access of cellular proteins to the viral genome RNA, e.g. initiation factors of protein synthesis. (3) In a following step, ribosomal 60S subunits bind to the complex and lead to core disassembly with a concomitant transfer of core protein or of core protein fragments to the 28S rRNA. The linker region may be involved in this transfer. (4) During the later stages of virus multiplication, cellular components involved in step (2) and/or in step (3) are inactivated. This inactivation might involve the binding of newly synthesised core protein to 28S rRNA. (5) Unprimed cores, e.g. core particles containing the linker region in an unexposed position, are assembled during virus multiplication. Priming of cores and inactivation of host-cell factors each represent a complete mechanism of regulation of core disassembly. Future experiments will show whether or not both processes are actually used. Since alphaviruses, e.g. Chikungunya virus, Ross River virus, Semliki Forest virus, and Sindbis virus, are human pathogens, these experiments are of practical relevance, since they might identify targets for antiviral chemotherapy.

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References

  1. Cheng R, Kuhn R, Olson N, Rossmann M, Baker T (1995) Nucleocapsid and glycoprotein organization in an enveloped virus. Cell 80:621–630

    Article  PubMed  CAS  Google Scholar 

  2. Choi HK, Tong I, Minor W, Dumas P, Boege U, Rossmann MG, Wengler G (1991) Structure of Sindbis virus core protein reveals a chymotrypsin-like serine proteinase and the organization of the virion. Nature 354:37–43

    Article  PubMed  CAS  Google Scholar 

  3. Coombs K, Brown B, Brown DT (1984) Evidence for a change in capsid morphology during Sindbis virus envelopment. Virus Res 1:297–302

    Article  PubMed  CAS  Google Scholar 

  4. Forsell K, Griffiths G, Garoff H (1996) Preformed cytoplasmic nucleocapsids are not necessary for alphavirus budding. EMBO J 15:6495–6505

    PubMed  CAS  Google Scholar 

  5. Forsell K, Xing L, Kozlovska T, Cheng RH, Garoff H (2000) Membrane proteins organize a symmetrical virus. EMBO J 19:5081–5091

    Article  PubMed  CAS  Google Scholar 

  6. Froshauer S, Kartenbeck J, Helenius A (1988) Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes. J Cell Biol 107:2075–2086

    Article  PubMed  CAS  Google Scholar 

  7. Garoff H, Sjöberg M, Cheng RH (2004) Budding of alphaviruses. Virus Res 106:103–116

    Article  PubMed  CAS  Google Scholar 

  8. Gaspar LP, Terezan AF, Pinheiro AS, Foguel D, Rebello MA, Silva JL (2001) The metastable state of nucleocapsids of enveloped viruses as probed by high hydrostatic pressure. J Biol Chem 276:7415–7421

    Article  PubMed  CAS  Google Scholar 

  9. Geigenmüller-Gnirke U, Nitschko H, Schlesinger S (1993) Deletion analysis of the capsid protein of Sindbis virus: identification of the RNA binding region. J Virol 67:1620–1626

    PubMed  Google Scholar 

  10. Glanville N, Ulmanen I (1976) Biological activity of in vitro synthesized protein: binding of Semliki Forest virus capsid protein to the large ribosomal subunit. Biochem Biophys Res Commun 71:393–399

    Article  PubMed  CAS  Google Scholar 

  11. Harrison SC (2007) Principles of virus structure. In: Fields BN, Knipe DM, Howly PM (eds) Virology. Lippincott, PA, pp 59–98

    Google Scholar 

  12. Hase T, Summers PL, Eckels KH (1989) Flavivirus entry into cultured mosquito cells and human peripheral blood monocytes. Arch Virol 104:129–143

    Article  PubMed  CAS  Google Scholar 

  13. Helenius A, Kartenbeck J, Simons K, Fries E (1980) On the entry of Semliki Forest virus into BHK–21 cells. J Cell Biol 84:404–420

    Article  PubMed  CAS  Google Scholar 

  14. Helenius A (1984) Semliki Forest virus penetration from endosomes: a morphological study. Biol Cell 51:181–185

    PubMed  CAS  Google Scholar 

  15. Käsermann F, Kempf C (1996) Low pH-induced pore formation by spike proteins of enveloped viruses. J Gen Virol 77:3025–3032

    Article  PubMed  Google Scholar 

  16. Kielian M (2006) Class II virus membrane fusion proteins. Virology 344:38–47

    Article  PubMed  CAS  Google Scholar 

  17. Koschinski A, Wengler G, Wengler G, Repp H (2003) The membrane proteins of flaviviruses form ion-permeable pores in the target membrane after fusion: identification of the pores and analysis of their possible role in virus infection. J Gen Virol 84:1711–1721

    Article  PubMed  CAS  Google Scholar 

  18. Koschinski A, Wengler G, Wengler G, Repp H (2005) Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J Gen Virol 86:3311–3320

    Article  PubMed  CAS  Google Scholar 

  19. Kuhn RJ (2007) Togaviridae: the viruses and their replication. In: Fields BN, Knipe DM, Howley PM (eds) Virology. Lippincott, PA, pp 1001–1022

    Google Scholar 

  20. Lanzrein M, Weingart R, Kempf C (1993) PH-dependent pore formation in Semliki Forest virus-infected aedes albopictus cells. Virology 193:296–302

    Article  PubMed  CAS  Google Scholar 

  21. Lanzrein M, Schlegel A, Kempf C (1994) Entry and uncoating of enveloped viruses. Biochem J 302:313–320

    PubMed  CAS  Google Scholar 

  22. Mancini EJ, Clarke M, Gowen BE, Rutten TSD (2000) Cryoelectron-microscopy reveals the functional organization of an enveloped virus, Semliki Forest virus. Mol Cell 5:255–266

    Article  PubMed  CAS  Google Scholar 

  23. Mrkic B, Kempf C (1996) The fragmentation of incoming Semliki Forest virus nucleocapsids in mosquito (Aedes albopictus) cells might be coupled to virion uncoating. Arch Virol 141:1805–1821

    Article  PubMed  CAS  Google Scholar 

  24. Mrkic B, Tetaz T, Kempf C (1997) Cleavage of incoming Semliki Forest virus capsid protein within the endocytotic pathway: a feature common to both invertebrate and mammalian cells. Arch Virol 142:1895–1902

    Article  PubMed  CAS  Google Scholar 

  25. Mukhopadhyay S, Chipman PR, Hong EM, Kuhn RJ, Rossmann MG (2002) In vitro-assembled alphavirus core-like particles maintain a structure to that of nucleocapsid cores in mature virus. J Virol 76:11128–11132

    Article  PubMed  CAS  Google Scholar 

  26. Mukhopadhyay S, Zhang W, Gabler S et al (2006) Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses. Structure 14:63–73

    Article  PubMed  CAS  Google Scholar 

  27. Nyfeler S, Senn K, Kempf C (2001) Expression of Semliki Forest virus E1 protein in Escherichia coli. J Biol Chem 276:15453–15457

    Article  PubMed  CAS  Google Scholar 

  28. Omar A, Koblet H (1988) Semliki Forest virus particles containing only the E1 envelope glycoprotein are infectious and can induce cell-cell fusion. Virology 166:17–23

    Article  PubMed  CAS  Google Scholar 

  29. Owen KE, Kuhn RJ (1996) Identification of a region in the Sindbis virus nucleocapsid protein that is involved in specificity of RNA encapsidation. J Virol 70:2757–2763

    PubMed  CAS  Google Scholar 

  30. Paredes AM, Brown DT, Rothnagel R, Chiu W, Schoepp RJ, Johnston RE, Prasad BVV (1993) Three-dimensional structure of a membrane-containing virus. Proc Natl Acad Sci USA 90:9095–9099

    Article  PubMed  CAS  Google Scholar 

  31. Paredes AM, Ferreira D, Horton M et al (2004) Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324:373–386

    Article  PubMed  CAS  Google Scholar 

  32. Ranki M, Ulmanen I, Kääriäinen L (1979) Semliki Forest virus-specific nonstructural protein is associated with ribosomes. FEBS Lett 108:299–302

    Article  PubMed  CAS  Google Scholar 

  33. Rikkonen M, Peränen J, Kääriäinen L (1992) Nuclear and nucleolar targeting signals of Semliki Forest virus nonstructural protein nsP2. Virology 189:462–473

    Article  PubMed  CAS  Google Scholar 

  34. Schlegel A, Omar A, Jentsch P, Morell A, Kempf C (1991) Semliki Forest virus envelope proteins function as proton channels. Biosci Rep 11:243–255

    Article  PubMed  CAS  Google Scholar 

  35. Schlegel A, Schaller J, Jentsch P, Kempf C (1993) Semliki Forest virus core protein cleavage: its possible role in nucleocapsid disassembly. Biosci Rep 13:333–347

    Article  PubMed  CAS  Google Scholar 

  36. Schlesinger S, Schlesinger MJ (2001) Togaviridae: the viruses and their replication. In: Fields BN, Knipe DM, Howley PM (eds) Virology. Lippincott, PA, pp 895–916

    Google Scholar 

  37. Singh IR, Helenius A (1992) Role of ribosomes in Semliki Forest virus nucleocapsid uncoating. J Virol 66:7049–7058

    PubMed  CAS  Google Scholar 

  38. Singh IR, Suomalainen M, Varadarajan S, Garoff H, Helenius A (1997) Multiple mechanisms for the inhibition of entry and uncoating of superinfecting Semliki Forest virus. Virology 231:59–71

    Article  PubMed  CAS  Google Scholar 

  39. Söderlund H, Kääriäinen L, Von Bonsdorff C-H, Weckstein P (1972) Properties of Semliki Forest virus nucleocapsid II: an irreversible contraction by acid pH. Virology 47:753–760

    Article  PubMed  Google Scholar 

  40. Söderlund H, Ulmanen I (1977) Transient association of Semliki Forest virus capsid protein with ribosomes. J Virol 24:907–909

    PubMed  Google Scholar 

  41. Spyr CA, Käsermann F, Kempf C (1995) Identification of the pore forming element of Semliki Forest virus spikes. FEBS Lett 375:134–136

    Article  PubMed  CAS  Google Scholar 

  42. Strong RK, Harrison SC (1990) Proteolytic dissection of Sindbis virus core protein. J Virol 64:3992–3994

    PubMed  CAS  Google Scholar 

  43. Strauss JH, Strauss EG (1994) Gene expression replication, and evolution. Microbiol Rev 58:491–562

    PubMed  CAS  Google Scholar 

  44. Ulmanen I, Söderlund H, Kääriäinen L (1976) Semliki Forest virus capsid protein associates with the 60S ribosomal subunit in infected cells. J Virol 20:203–210

    PubMed  CAS  Google Scholar 

  45. Ulmanen I, Söderlund H, Kääriäinen L (1979) Role of protein synthesis in the assembly of Semliki Forest virus nucleocapsid. Virology 99:265–276

    Article  PubMed  CAS  Google Scholar 

  46. Wang G, Hernandez R, Weninger K, Brown DT (2007) Infection of cells by Sindbis virus at low temperature. Virology 362:461–467

    Article  PubMed  CAS  Google Scholar 

  47. Warrier R, Linger BR, Golden BL, Kuhn R (2008) Role of Sindbis virus capsid protein region II in nucleocapsid core assembly and encapsidation of genomic RNA. J Virol 82:4461–4470

    Article  PubMed  CAS  Google Scholar 

  48. Wengler G, Boege U, Wengler G, Bischoff H, Wahn K (1982) The core protein of the alphavirus Sindbis virus assembles into core-like nucleoproteins with the viral genome RNA and with other single-stranded nucleic acids in vitro. Virology 118:401–410

    Article  PubMed  CAS  Google Scholar 

  49. Wengler G, Wengler G (1984) Identification of a transfer of viral core protein to cellular ribosomes during the early stages of alphavirus infection. Virology 134:435–442

    Article  PubMed  CAS  Google Scholar 

  50. Wengler G, Wengler G, Boege U, Wahn K (1984) Establishment and analysis of a system which allows assembly and disassembly of alphavirus core-like particles under physiological conditions in vitro. Virology 132:401–410

    Article  PubMed  CAS  Google Scholar 

  51. Wengler G, Würkner D, Wengler G (1992) Identification of a sequence element in the alphavirus core protein which mediates interaction of cores with ribosomes and the disassembly of cores. Virology 191:880–888

    Article  PubMed  CAS  Google Scholar 

  52. Wengler G, Gros C, Wengler G (1996) Analyses of the role of structural changes in the regulation of uncoating and assembly of alphavirus cores. Virology 222:123–132

    Article  PubMed  CAS  Google Scholar 

  53. Wengler G, Wengler G (2002) In vitro analyses of factors involved in the disassembly of Sindbis virus cores by 60S ribosomal subunits identify a possible role of low pH in this process. J Gen Virol 83:2417–2426

    PubMed  CAS  Google Scholar 

  54. Wengler G, Koschinski A, Wengler G, Dreyer F (2003) Entry of alphaviruses at the plasma membrane converts the viral surface proteins into an ion-permeable pore that can be detected by electrophysiological analyses of whole-cell membrane currents. J Gen Virol 84:173–181

    Article  PubMed  CAS  Google Scholar 

  55. White J, Helenius A (1980) PH-dependent fusion between the Semliki Forest virus membrane and liposomes. Proc Natl Acad Sci USA 77:3273–3277

    Article  PubMed  CAS  Google Scholar 

  56. White J, Kartenbeck J, Helenius A (1980) Fusion of Semliki Forest virus with the plasma membrane can be induced by low pH. J Cell Biol 87:264–272

    Article  PubMed  CAS  Google Scholar 

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  1. Institut für Virologie, Fachbereich Veterinärmedizin, Justus-Liebig-Universität, 35392, Giessen, Germany

    Gerd Wengler

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Wengler, G. The regulation of disassembly of alphavirus cores. Arch Virol 154, 381–390 (2009). https://doi.org/10.1007/s00705-009-0333-9

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  • DOI: https://doi.org/10.1007/s00705-009-0333-9

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