1887

Abstract

We have previously reported a system for packaging tick-borne encephalitis (TBE) virus subgenomic replicon RNAs into single-round infectious virus-like particles (VLPs) by using expression of viral C/prM/E structural proteins. In this study, the -packaging system was applied to the generation of chimeric VLPs with mosquito-borne Japanese encephalitis (JE) virus. Although -expression of TBE virus C and JE virus prM/E proteins resulted in the secretion of VLPs, the expression of JE virus C/prM/E proteins did not lead to the secretion of VLPs, suggesting that homologous interaction between C and non-structural proteins or the genomic RNA is important for efficient assembly of infectious particles. Neutralization testing showed that the antigenic characteristics of the VLPs were similar to those of the native virus. Furthermore, the infectivities of the TBE virus- and JE virus-enveloped VLPs for the ISE6 tick cell line and C6/36 mosquito cell line were investigated. The VLPs were able to enter only those cells that were derived from the natural vectors for the respective viruses. TBE virus replicon RNA packaged in VLPs produced TBE virus non-structural proteins in tick cells, but could neither replicate nor produce viral proteins in mosquito cells. These findings indicate the importance of specific cellular factors for virus entry and replication during flavivirus infection of arthropods. These results demonstrate that chimeric VLPs are useful tools for the study of viral genome packaging and cellular factors involved in vector specificity, with the additional safety aspect that these chimeric VLPs can be used instead of full-length chimeric viruses.

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2008-01-01
2024-04-19
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References

  1. Allison S. L., Stadler K., Mandl C. W., Kunz C., Heinz F. X. 1995; Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in soluble and particulate form. J Virol 69:5816–5820
    [Google Scholar]
  2. Amberg S. M., Rice C. M. 1999; Mutagenesis of the NS2B-NS3-mediated cleavage site in the flavivirus capsid protein demonstrates a requirement for coordinated processing. J Virol 73:8083–8094
    [Google Scholar]
  3. Amberg S. M., Nestorowicz A., McCourt D. W., Rice C. M. 1994; NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol 68:3794–3802
    [Google Scholar]
  4. Caufour P. S., Motta M. C., Yamamura A. M., Vazquez S., Ferreira I. I., Jabor A. V., Bonaldo M. C., Freire M. S., Galler R. 2001; Construction, characterization and immunogenicity of recombinant yellow fever 17D-dengue type 2 viruses. Virus Res 79:1–14 [CrossRef]
    [Google Scholar]
  5. Chambers T. J., Hahn C. S., Galler R., Rice C. M. 1990; Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44:649–688 [CrossRef]
    [Google Scholar]
  6. Chambers T. J., Nestorowicz A., Mason P. W., Rice C. M. 1999; Yellow fever/Japanese encephalitis chimeric viruses: construction and biological properties. J Virol 73:3095–3101
    [Google Scholar]
  7. Gaunt M. W., Sall A. A., de Lamballerie X., Falconar A. K., Dzhivanian T. I., Gould E. A. 2001; Phylogenetic relationships of flaviviruses correlate with their epidemiology, disease association and biogeography. J Gen Virol 82:1867–1876
    [Google Scholar]
  8. Gehrke R., Ecker M., Aberle S. W., Allison S. L., Heinz F. X., Mandl C. W. 2003; Incorporation of tick-borne encephalitis virus replicons into virus-like particles by a packaging cell line. J Virol 77:8924–8933 [CrossRef]
    [Google Scholar]
  9. Gould E. A., de Lamballerie X., Zanotto P. M., Holmes E. C. 2003; Origins, evolution, and vector/host coadaptations within the genus Flavivirus . Adv Virus Res 59:277–314
    [Google Scholar]
  10. Gritsun T. S., Venugopal K., Zanotto P. M., Mikhailov M. V., Sall A. A., Holmes E. C., Polkinghorne I., Frolova T. V., Pogodina V. V. other authors 1997; Complete sequence of two tick-borne flaviviruses isolated from Siberia and the UK: analysis and significance of the 5′ and 3′-UTRs. Virus Res 49:27–39 [CrossRef]
    [Google Scholar]
  11. Guirakhoo F., Weltzin R., Chambers T. J., Zhang Z. X., Soike K., Ratterree M., Arroyo J., Georgakopoulos K., Catalan J., Monath T. P. 2000; Recombinant chimeric yellow fever-dengue type 2 virus is immunogenic and protective in nonhuman primates. J Virol 74:5477–5485 [CrossRef]
    [Google Scholar]
  12. Guirakhoo F., Arroyo J., Pugachev K. V., Miller C., Zhang Z. X., Weltzin R., Georgakopoulos K., Catalan J., Ocran S. other authors 2001; Construction, safety, and immunogenicity in nonhuman primates of a chimeric yellow fever-dengue virus tetravalent vaccine. J Virol 75:7290–7304 [CrossRef]
    [Google Scholar]
  13. Hardy J. L., Houk E. J., Kramer L. D., Reeves W. C. 1983; Intrinsic factors affecting vector competence of mosquitoes for arboviruses. Annu Rev Entomol 28:229–262 [CrossRef]
    [Google Scholar]
  14. Harvey T. J., Liu W. J., Wang X. J., Linedale R., Jacobs M., Davidson A., Le T. T., Anraku I., Suhrbier A. other authors 2004; Tetracycline-inducible packaging cell line for production of flavivirus replicon particles. J Virol 78:531–538 [CrossRef]
    [Google Scholar]
  15. Hayasaka D., Yoshii K., Ueki T., Iwasaki T., Takashima I. 2004; Sub-genomic replicons of Tick-borne encephalitis virus. Arch Virol 149:1245–1256 [CrossRef]
    [Google Scholar]
  16. Heinz F. X., Stiasny K., Allison S. L. 2004; The entry machinery of flaviviruses. Arch Virol Suppl133–137
    [Google Scholar]
  17. Huang C. Y., Butrapet S., Pierro D. J., Chang G. J., Hunt A. R., Bhamarapravati N., Gubler D. J., Kinney R. M. 2000; Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine. J Virol 74:3020–3028 [CrossRef]
    [Google Scholar]
  18. Igarashi A. 1978; Isolation of a Singh's Aedes albopictus cell clone sensitive to dengue and chikungunya viruses. J Gen Virol 40:531–544 [CrossRef]
    [Google Scholar]
  19. Khromykh A. A., Westaway E. G. 1997; Subgenomic replicons of the flavivirus Kunjin: construction and applications. J Virol 71:1497–1505
    [Google Scholar]
  20. Khromykh A. A., Varnavski A. N., Westaway E. G. 1998; Encapsidation of the flavivirus kunjin replicon RNA by using a complementation system providing Kunjin virus structural proteins in trans. J Virol 72:5967–5977
    [Google Scholar]
  21. Khromykh A. A., Sedlak P. L., Westaway E. G. 2000; cis - and trans -acting elements in flavivirus RNA replication. J Virol 74:3253–3263 [CrossRef]
    [Google Scholar]
  22. Khromykh A. A., Varnavski A. N., Sedlak P. L., Westaway E. G. 2001; Coupling between replication and packaging of flavivirus RNA: evidence derived from the use of DNA-based full-length cDNA clones of Kunjin virus. J Virol 75:4633–4640 [CrossRef]
    [Google Scholar]
  23. 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]
  24. 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]
  25. Konishi E., Yamaoka M., Khin Sane W., Kurane I., Mason P. W. 1998; Induction of protective immunity against Japanese encephalitis in mice by immunization with a plasmid encoding Japanese encephalitis virus premembrane and envelope genes. J Virol 72:4925–4930
    [Google Scholar]
  26. Konishi E., Fujii A., Mason P. W. 2001; Generation and characterization of a mammalian cell line continuously expressing Japanese encephalitis virus subviral particles. J Virol 75:2204–2212 [CrossRef]
    [Google Scholar]
  27. Kramer L. D., Ebel G. D. 2003; Dynamics of flavivirus infection in mosquitoes. Adv Virus Res 60:187–232
    [Google Scholar]
  28. Kummerer B. M., Rice C. M. 2002; Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles. J Virol 76:4773–4784 [CrossRef]
    [Google Scholar]
  29. Kuno G., Chang G. J., Tsuchiya K. R., Karabatsos N., Cropp C. B. 1998; Phylogeny of the genus Flavivirus . J Virol 72:73–83
    [Google Scholar]
  30. Lawrie C. H., Uzcategui N. Y., Armesto M., Bell-Sakyi L., Gould E. A. 2004; Susceptibility of mosquito and tick cell lines to infection with various flaviviruses. Med Vet Entomol 18:268–274 [CrossRef]
    [Google Scholar]
  31. Liu W. J., Sedlak P. L., Kondratieva N., Khromykh A. A. 2002; Complementation analysis of the flavivirus Kunjin NS3 and NS5 proteins defines the minimal regions essential for formation of a replication complex and shows a requirement of NS3 in cis for virus assembly. J Virol 76:10766–10775 [CrossRef]
    [Google Scholar]
  32. Lobigs M. 1993; Flavivirus premembrane protein cleavage and spike heterodimer secretion require the function of the viral proteinase NS3. Proc Natl Acad Sci U S A 90:6218–6222 [CrossRef]
    [Google Scholar]
  33. 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]
  34. 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]
  35. Mandl C. W., Kunz C., Heinz F. X. 1991; Presence of poly(A) in a flavivirus: significant differences between the 3′ noncoding regions of the genomic RNAs of tick-borne encephalitis virus strains. J Virol 65:4070–4077
    [Google Scholar]
  36. 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]
  37. Mathenge E. G., Parquet Mdel C., Funakoshi Y., Houhara S., Wong P. F., Ichinose A., Hasebe F., Inoue S., Morita K. 2004; Fusion PCR generated Japanese encephalitis virus/dengue 4 virus chimera exhibits lack of neuroinvasiveness, attenuated neurovirulence, and a dual-flavi immune response in mice. J Gen Virol 85:2503–2513 [CrossRef]
    [Google Scholar]
  38. Mizutani T., Kobayashi M., Eshita Y., Shirato K., Kimura T., Ako Y., Miyoshi H., Takasaki T., Kurane I. other authors 2003; Involvement of the JNK-like protein of the Aedes albopictus mosquito cell line, C6/36, in phagocytosis, endocytosis and infection of West Nile virus. Insect Mol Biol 12:491–499 [CrossRef]
    [Google Scholar]
  39. Molenkamp R., Kooi E. A., Lucassen M. A., Greve S., Thijssen J. C., Spaan W. J., Bredenbeek P. J. 2003; Yellow fever virus replicons as an expression system for hepatitis C virus structural proteins. J Virol 77:1644–1648 [CrossRef]
    [Google Scholar]
  40. Monath T. P., Soike K., Levenbook I., Zhang Z. X., Arroyo J., Delagrave S., Myers G., Barrett A. D., Shope R. E. other authors 1999; Recombinant, chimaeric live, attenuated vaccine (ChimeriVax) incorporating the envelope genes of Japanese encephalitis (SA14–14–2) virus and the capsid and nonstructural genes of yellow fever (17D) virus is safe, immunogenic and protective in non-human primates. Vaccine 17:1869–1882 [CrossRef]
    [Google Scholar]
  41. Munderloh U. G., Liu Y., Wang M., Chen C., Kurtti T. J. 1994; Establishment, maintenance and description of cell lines from the tick Ixodes scapularis . J Parasitol 80:533–543 [CrossRef]
    [Google Scholar]
  42. 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]
  43. Nuttall P. A., Labuda M. 2003; Dynamics of infection in tick vectors and at the tick-host interface. Adv Virus Res 60:233–272
    [Google Scholar]
  44. Pang X., Zhang M., Dayton A. I. 2001; Development of dengue virus type 2 replicons capable of prolonged expression in host cells. BMC Microbiol 1:18 [CrossRef]
    [Google Scholar]
  45. Pletnev A. G., Men R. 1998; Attenuation of the Langat tick-borne flavivirus by chimerization with mosquito-borne flavivirus dengue type 4. Proc Natl Acad Sci U S A 95:1746–1751 [CrossRef]
    [Google Scholar]
  46. Pletnev A. G., Bray M., Huggins J., Lai C. J. 1992; Construction and characterization of chimeric tick-borne encephalitis/dengue type 4 viruses. Proc Natl Acad Sci U S A 89:10532–10536 [CrossRef]
    [Google Scholar]
  47. Pletnev A. G., Putnak R., Speicher J., Wagar E. J., Vaughn D. W. 2002; West Nile virus/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy. Proc Natl Acad Sci U S A 99:3036–3041 [CrossRef]
    [Google Scholar]
  48. Proutski V., Gould E. A., Holmes E. C. 1997; Secondary structure of the 3′ untranslated region of flaviviruses: similarities and differences. Nucleic Acids Res 25:1194–1202 [CrossRef]
    [Google Scholar]
  49. Rauscher S., Flamm C., Mandl C. W., Heinz F. X., Stadler P. F. 1997; Secondary structure of the 3′-noncoding region of flavivirus genomes: comparative analysis of base pairing probabilities. RNA 3:779–791
    [Google Scholar]
  50. Sato T., Takamura C., Yasuda A., Miyamoto M., Kamogawa K., Yasui K. 1993; High-level expression of the Japanese encephalitis virus E protein by recombinant vaccinia virus and enhancement of its extracellular release by the NS3 gene product. Virology 192:483–490 [CrossRef]
    [Google Scholar]
  51. Scholle F., Girard Y. A., Zhao Q., Higgs S., Mason P. W. 2004; trans -packaged West Nile virus-like particles: infectious properties in vitro and in infected mosquito vectors. J Virol 78:11605–11614 [CrossRef]
    [Google Scholar]
  52. Shi P. Y., Tilgner M., Lo M. K. 2002; Construction and characterization of subgenomic replicons of New York strain of West Nile virus. Virology 296:219–233 [CrossRef]
    [Google Scholar]
  53. Stocks C. E., Lobigs M. 1998; Signal peptidase cleavage at the flavivirus C-prM junction: dependence on the viral NS2B-3 protease for efficient processing requires determinants in C, the signal peptide, and prM. J Virol 72:2141–2149
    [Google Scholar]
  54. Takashima I., Morita K., Chiba M., Hayasaka D., Sato T., Takezawa C., Igarashi A., Kariwa H., Yoshimatsu K. other authors 1997; A case of tick-borne encephalitis in Japan and isolation of the virus. J Clin Microbiol 35:1943–1947
    [Google Scholar]
  55. Yamshchikov V. F., Compans R. W. 1995; Formation of the flavivirus envelope: role of the viral NS2B-NS3 protease. J Virol 69:1995–2003
    [Google Scholar]
  56. Yamshchikov V. F., Trent D. W., Compans R. W. 1997; Upregulation of signalase processing and induction of prM-E secretion by the flavivirus NS2B-NS3 protease: roles of protease components. J Virol 71:4364–4371
    [Google Scholar]
  57. Yoshii K., Konno A., Goto A., Nio J., Obara M., Ueki T., Hayasaka D., Mizutani T., Kariwa H., Takashima I. 2004; Single point mutation in tick-borne encephalitis virus prM protein induces a reduction of virus particle secretion. J Gen Virol 85:3049–3058 [CrossRef]
    [Google Scholar]
  58. Yoshii K., Hayasaka D., Goto A., Kawakami K., Kariwa H., Takashima I. 2005; Packaging the replicon RNA of the Far-Eastern subtype of tick-borne encephalitis virus into single-round infectious particles; development of a heterologous gene delivery system. Vaccine 23:3946–3956 [CrossRef]
    [Google Scholar]
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