1887

Abstract

Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum (ER) and are secreted through the vesicle transport pathway. Virus envelope proteins play important roles in this process. In this study, the effect of mutations in the envelope proteins of tick-borne encephalitis (TBE) virus on secretion of virus-like particles (VLPs), using a recombinant plasmid expression system was analysed. It was found that a single point mutation at position 63 in prM induces a reduction in secretion of VLPs. The mutation in prM did not affect the folding of the envelope proteins, and chaperone-like activity of prM was maintained. As observed by immunofluorescence microscopy, viral envelope proteins with the mutation in prM were scarce in the Golgi complex, and accumulated in the ER. Electron microscopic analysis of cells expressing the mutated prM revealed that many tubular structures were present in the lumen. The insertion of the prM mutation at aa 63 into the viral genome reduced the production of infectious virus particles. This data suggest that prM plays a crucial role in the virus budding process.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80169-0
2004-10-01
2024-03-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/10/vir853049.html?itemId=/content/journal/jgv/10.1099/vir.0.80169-0&mimeType=html&fmt=ahah

References

  1. Allison S. L., Schalich J., Stiasny K., Mandl C. W., Kunz C., Heinz F. X. 1995a; Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol 69:695–700
    [Google Scholar]
  2. Allison S. L., Stadler K., Mandl C. W., Kunz C., Heinz F. X. 1995b; Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in soluble and particulate form. J Virol 69:5816–5820
    [Google Scholar]
  3. Allison S. L., Stiasny K., Stadler K., Mandl C. W., Heinz F. X. 1999; Mapping of functional elements in the stem-anchor region of tick-borne encephalitis virus envelope protein E. J Virol 73:5605–5612
    [Google Scholar]
  4. Allison S. L., Schalich J., Stiasny K., Mandl C. W., Heinz F. X. 2001; Mutational evidence for an internal fusion peptide in flavivirus envelope protein E. J Virol 75:4268–4275 [CrossRef]
    [Google Scholar]
  5. Corver J., Ortiz A., Allison S. L., Schalich J., Heinz F. X., Wilschut J. 2000; Membrane fusion activity of tick-borne encephalitis virus and recombinant subviral particles in a liposomal model system. Virology 269:37–46 [CrossRef]
    [Google Scholar]
  6. de Haan C. A., Kuo L., Masters P. S., Vennema H., Rottier P. J. 1998; Coronavirus particle assembly: primary structure requirements of the membrane protein. J Virol 72:6838–6850
    [Google Scholar]
  7. Elshuber S., Allison S. L., Heinz F. X., Mandl C. W. 2003; Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus. J Gen Virol 84:183–191 [CrossRef]
    [Google Scholar]
  8. Garoff H., Hewson R., Opstelten D. J. 1998; Virus maturation by budding. Microbiol Mol Biol Rev 62:1171–1190
    [Google Scholar]
  9. Gritsun T. S., Lisak V. M., Liapustin V. N., Korolev M. B., Lashkevich V. A. 1989; Slowly-sedimenting hemagglutinin of the tick-borne encephalitis virus. Vopr Virusol 34:449–454 (in Russian
    [Google Scholar]
  10. Hayasaka D., Gritsun T. S., Yoshii K. 7 other authors 2004; Amino acid changes responsible for attenuation of virus neurovirulence in an infectious cDNA clone of the Oshima strain of Tick-borne encephalitis virus . J Gen Virol 85:1007–1018 [CrossRef]
    [Google Scholar]
  11. Heinz F., Kunz C. 1977; Concentration and purification of tick-borne encephalitis virus grown in suspensions of chick embryo cells. Acta Virol 21:301–307
    [Google Scholar]
  12. Heinz F. X., Mandl C. W. 1993; The molecular biology of tick-borne encephalitis virus. Review article. APMIS 101:735–745 [CrossRef]
    [Google Scholar]
  13. Heinz F. X., Allison S. L. 2000; Structures and mechanisms in flavivirus fusion. Adv Virus Res 55:231–269
    [Google Scholar]
  14. Ishak R., Tovey D. G., Howard C. R. 1988; Morphogenesis of yellow fever virus 17D in infected cell cultures. J Gen Virol 69:325–335 [CrossRef]
    [Google Scholar]
  15. Jin H., Leser G. P., Zhang J., Lamb R. A. 1997; Influenza virus hemagglutinin and neuraminidase cytoplasmic tails control particle shape. EMBO J 16:1236–1247 [CrossRef]
    [Google Scholar]
  16. Kail M., Hollinshead M., Ansorge W., Pepperkok R., Frank R., Griffiths G., Vaux D. 1991; The cytoplasmic domain of alphavirus E2 glycoprotein contains a short linear recognition signal required for viral budding. EMBO J 10:2343–2351
    [Google Scholar]
  17. Keen J. H., Willingham M. C., Pastan I. H. 1979; Clathrin-coated vesicles: isolation, dissociation and factor-dependent reassociation of clathrin baskets. Cell 16:303–312 [CrossRef]
    [Google Scholar]
  18. Komoro K., Hayasaka D., Mizutani T., Kariwa H., Takashima I. 2000; Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus. Microbiol Immunol 44:533–536 [CrossRef]
    [Google Scholar]
  19. Konishi E., Mason P. W. 1993; Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein. J Virol 67:1672–1675
    [Google Scholar]
  20. Konishi E., Pincus S., Paoletti E., Shope R. E., Burrage T., Mason P. W. 1992; Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal JEV infection. Virology 188:714–720 [CrossRef]
    [Google Scholar]
  21. Kuhn R. J., Zhang W., Rossmann M. G. 9 other authors 2002; Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108:717–725 [CrossRef]
    [Google Scholar]
  22. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685 [CrossRef]
    [Google Scholar]
  23. Lindenbach B. D., Rice C. M. 2001; Flaviviridae : the viruses and their replication. In Fields Virology , 4th edn. pp  991–1041 Edited by Knipe D. M., Howley P. M. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  24. Linstedt A. D., Hauri H. P. 1993; Giantin, a novel conserved Golgi membrane protein containing a cytoplasmic domain of at least 350 kDa. Mol Biol Cell 4:679–693 [CrossRef]
    [Google Scholar]
  25. Lorenz I. C., Allison S. L., Heinz F. X., Helenius A. 2002; Folding and dimerization of tick-borne encephalitis virus envelope proteins prM and E in the endoplasmic reticulum. J Virol 76:5480–5491 [CrossRef]
    [Google Scholar]
  26. Lorenz I. C., Kartenbeck J., Mezzacasa A., Allison S. L., Heinz F. X., Helenius A. 2003; Intracellular assembly and secretion of recombinant subviral particles from tick-borne encephalitis virus. J Virol 77:4370–4382 [CrossRef]
    [Google Scholar]
  27. Mackenzie J. M., Westaway E. G. 2001; Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 75:10787–10799 [CrossRef]
    [Google Scholar]
  28. Mandl C. W., Guirakhoo F., Holzmann H., Heinz F. X., Kunz C. 1989; Antigenic structure of the flavivirus envelope protein E at the molecular level, using tick-borne encephalitis virus as a model. J Virol 63:564–571
    [Google Scholar]
  29. Mason P. W., Pincus S., Fournier M. J., Mason T. L., Shope R. E., Paoletti E. 1991; Japanese encephalitis virus-vaccinia recombinants produce particulate forms of the structural membrane proteins and induce high levels of protection against lethal JEV infection. Virology 180:294–305 [CrossRef]
    [Google Scholar]
  30. McNiven M. A. 1998; Dynamin: a molecular motor with pinchase action. Cell 94:151–154 [CrossRef]
    [Google Scholar]
  31. Michalak M., Milner R. E., Burns K., Opas M. 1992; Calreticulin. Biochem J 285:681–692
    [Google Scholar]
  32. Mitnaul L. J., Castrucci M. R., Murti K. G., Kawaoka Y. 1996; The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication. J Virol 70:873–879
    [Google Scholar]
  33. Niwa H., Yamamura K., Miyazaki J. 1991; Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108:193–199 [CrossRef]
    [Google Scholar]
  34. Ocazionez Jimenez R., Lopes da Fonseca B. A. 2000; Recombinant plasmid expressing a truncated dengue-2 virus E protein without co-expression of prM protein induces partial protection in mice. Vaccine 19:648–654 [CrossRef]
    [Google Scholar]
  35. Op De Beeck A., Molenkamp R., Caron M., Ben Younes A., Bredenbeek P., Dubuisson J. 2003; Role of the transmembrane domains of prM and E proteins in the formation of yellow fever virus envelope. J Virol 77:813–820 [CrossRef]
    [Google Scholar]
  36. Owen K. E., Kuhn R. J. 1997; Alphavirus budding is dependent on the interaction between the nucleocapsid and hydrophobic amino acids on the cytoplasmic domain of the E2 envelope glycoprotein. Virology 230:187–196 [CrossRef]
    [Google Scholar]
  37. Owens R. J., Rose J. K. 1993; Cytoplasmic domain requirement for incorporation of a foreign envelope protein into vesicular stomatitis virus. J Virol 67:360–365
    [Google Scholar]
  38. Patzer E. J., Nakamura G. R., Simonsen C. C., Levinson A. D., Brands R. 1986; Intracellular assembly and packaging of hepatitis B surface antigen particles occur in the endoplasmic reticulum. J Virol 58:884–892
    [Google Scholar]
  39. Rey F. A., Heinz F. X., Mandl C., Kunz C., Harrison S. C. 1995; The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375:291–298 [CrossRef]
    [Google Scholar]
  40. Rice C. M. 1996; Flaviviridae : the viruses and their replication. In Fields Virology . , 3rd edn. pp  931–959 Edited by Fields B. N., Knipe D. N., Howley P. M., Chanock R. M., Melnick J. L., Monath T. P., Roizman B., Straus S. E. Philadelphia: Lippincott-Raven;
  41. Schekman R., Orci L. 1996; Coat proteins and vesicle budding. Science 271:1526–1533 [CrossRef]
    [Google Scholar]
  42. Simon K., Lingappa V. R., Ganem D. 1988; Secreted hepatitis B surface antigen polypeptides are derived from a transmembrane precursor. J Cell Biol 107:2163–2168 [CrossRef]
    [Google Scholar]
  43. Stadler K., Allison S. L., Schalich J., Heinz F. X. 1997; Proteolytic activation of tick-borne encephalitis virus by furin. J Virol 71:8475–8481
    [Google Scholar]
  44. Stiasny K., Allison S. L., Mandl C. W., Heinz F. X. 2001; Role of metastability and acidic pH in membrane fusion by tick-borne encephalitis virus. J Virol 75:7392–7398 [CrossRef]
    [Google Scholar]
  45. Stiasny K., Allison S. L., Schalich J., Heinz F. X. 2002; Membrane interactions of the tick-borne encephalitis virus fusion protein E at low pH. J Virol 76:3784–3790 [CrossRef]
    [Google Scholar]
  46. Stocks C. E., Lobigs M. 1995; Posttranslational signal peptidase cleavage at the flavivirus C-prM junction in vitro. J Virol 69:8123–8126
    [Google Scholar]
  47. Takashima I., Morita K., Chiba M. 8 other authors 1997; A case of tick-borne encephalitis in Japan and isolation of the virus. J Clin Microbiol 35:1943–1947
    [Google Scholar]
  48. Vennema H., Godeke G. J., Rossen J. W., Voorhout W. F., Horzinek M. C., Opstelten D. J., Rottier P. J. 1996; Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes. EMBO J 15:2020–2028
    [Google Scholar]
  49. Wang J. J., Liao C. L., Chiou Y. W., Chiou C. T., Huang Y. L., Chen L. K. 1997; Ultrastructure and localization of E proteins in cultured neuron cells infected with Japanese encephalitis virus. Virology 238:30–39 [CrossRef]
    [Google Scholar]
  50. Wengler G., Wengler G. 1989; Cell-associated West Nile flavivirus is covered with E+pre-M protein heterodimers which are destroyed and reorganized by proteolytic cleavage during virus release. J Virol 63:2521–2526
    [Google Scholar]
  51. Whitt M. A., Chong L., Rose J. K. 1989; Glycoprotein cytoplasmic domain sequences required for rescue of a vesicular stomatitis virus glycoprotein mutant. J Virol 63:3569–3578
    [Google Scholar]
  52. Wieland F., Harter C. 1999; Mechanisms of vesicle formation: insights from the COP system. Curr Opin Cell Biol 11:440–446 [CrossRef]
    [Google Scholar]
  53. Yoshii K., Hayasaka D., Goto A. 8 other authors 2003; Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis. J Virol Methods 108:171–179 [CrossRef]
    [Google Scholar]
  54. Zhang W., Mukhopadhyay S., Pletnev S. V., Baker T. S., Kuhn R. J., Rossmann M. G. 2002; Placement of the structural proteins in Sindbis virus. J Virol 76:11645–11658 [CrossRef]
    [Google Scholar]
  55. Zhang Y., Corver J., Chipman P. R. 7 other authors 2003; Structures of immature flavivirus particles. EMBO J 22:2604–2613 [CrossRef]
    [Google Scholar]
  56. Zhao H., Lindqvist B., Garoff H., von Bonsdorff C. H., Liljestrom P. 1994; A tyrosine-based motif in the cytoplasmic domain of the alphavirus envelope protein is essential for budding. EMBO J 13:4204–4211
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80169-0
Loading
/content/journal/jgv/10.1099/vir.0.80169-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error