1887

Abstract

Chimeric (D2/WN) viruses containing the pre-membrane (prM) and envelope (E) proteins of (WN virus) and the capsid (C) and non-structural proteins of dengue 2 (DEN2) virus were used to evaluate the protective immunity elicited by either the flaviviral E protein or non-structural proteins. AG129 interferon-deficient mice, previously shown to be protected against lethal DEN1 or DEN2 viral infection after vaccination with a wild-type or candidate vaccine strain of DEN1 or DEN2 virus, respectively, were immunized with chimeric D2/WN virus and then challenged with DEN2 virus. D2/WN chimeric viruses were non-pathogenic in AG129 mice. These viruses elicited little anti-DEN E antibody, high levels of anti-DEN NS1 antibody and no or very low levels of DEN2 virus-neutralizing antibodies. Only 15 % of D2/WN-immunized mice survived challenge with DEN2 virus. However, their mean survival time increased by 11–14 days over non-immunized controls. These results suggest that, whilst the non-structural proteins were able to enhance mean survival times of AG129 mice, this protection was not as effective as protection mediated by the E protein.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81256-0
2006-02-01
2020-10-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/2/339.html?itemId=/content/journal/jgv/10.1099/vir.0.81256-0&mimeType=html&fmt=ahah

References

  1. Arroyo J., Guirakhoo F., Fenner S., Zhang Z.-X., Monath T. P., Chambers T. J. 2001; Molecular basis for attenuation of neurovirulence of a yellow fever virus/Japanese encephalitis virus chimera vaccine (ChimeriVax-JE). J Virol 75:934–942 [CrossRef]
    [Google Scholar]
  2. Blitvich B. J., Marlenee N. L., Hall R. A., Calisher C. H., Bowen R. A., Roehrig J. T., Komar N., Langevin S. A., Beaty B. J. 2003; Epitope-blocking enzyme-linked immunosorbent assays for the detection of serum antibodies to West Nile virus in multiple avian species. J Clin Microbiol 41:1041–1047 [CrossRef]
    [Google Scholar]
  3. Bray M., Zhao B., Markoff L., Eckels K. H., Chanock R. M., Lai C.-J. 1989; Mice immunized with recombinant vaccinia virus expressing dengue 4 virus structural proteins with or without nonstructural protein NS1 are protected against fatal dengue virus encephalitis. J Virol 63:2853–2856
    [Google Scholar]
  4. Bray M., Men R., Lai C.-J. 1996; Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge. J Virol 70:4162–4166
    [Google Scholar]
  5. Caufour P. S., Motta M. C. A., Yamamura A. M. Y., 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]
  6. Chambers T. J., Liang Y., Droll D. A., Schlesinger J. J., Davidson A. D., Wright P. J., Jiang X. 2003; Yellow fever virus/dengue-2 virus and yellow fever virus/dengue-4 virus chimeras: biological characterization, immunogenicity, and protection against dengue encephalitis in the mouse model. J Virol 77:3655–3668 [CrossRef]
    [Google Scholar]
  7. Falgout B., Bray M., Schlesinger J. J., Lai C.-J. 1990; Immunization of mice with recombinant vaccinia virus expressing authentic dengue virus nonstructural protein NS1 protects against lethal dengue virus encephalitis. J Virol 64:4356–4363
    [Google Scholar]
  8. Gubler D. J. 1998; Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11:480–496
    [Google Scholar]
  9. Guirakhoo F., Weltzin R., Chambers T. J. & 7 other authors 2000; Recombinant chimeric yellow fever-dengue type 2 virus is immunogenic and protective in nonhuman primates. J Virol 74:5477–5485 [CrossRef]
    [Google Scholar]
  10. Hall R. A., Brand T. N. H., Lobigs M., Sangster M. Y., Howard M. J., Mackenzie J. S. 1996; Protective immune responses to the E and NS1 proteins of Murray Valley encephalitis virus in hybrids of flavivirus-resistant mice. J Gen Virol 77:1287–1294 [CrossRef]
    [Google Scholar]
  11. Halstead S. B., O'Rourke E. J. 1977; Dengue virus and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 146:201–217 [CrossRef]
    [Google Scholar]
  12. Huang C. Y.-H., Butrapet S., Pierro D. J., Chang G.-J. 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]
  13. Huang C. Y.-H., Butrapet S., Tsuchyia K. R., Bhamarapravati N., Gubler D. J., Kinney R. M. 2003; Dengue 2 PDK-53 virus as a chimeric carrier for tetravalent dengue vaccine development. J Virol 77:11436–11447 [CrossRef]
    [Google Scholar]
  14. Huang C. Y.-H., Silengo S. J., Whiteman M. C., Kinney R. M. 2005; Chimeric dengue 2 PDK-53/West Nile NY99 viruses retain the phenotypic attenuation markers of the candidate PDK-53 vaccine virus and protect mice against lethal challenge with West Nile virus. J Virol 79:7300–7310 [CrossRef]
    [Google Scholar]
  15. Jacobs S. C., Stephenson J. R., Wilkinson G. W. G. 1992; High-level expression of the tick-borne encephalitis virus NS1 protein by using an adenovirus-based vector: protection elicited in a murine model. J Virol 66:2086–2095
    [Google Scholar]
  16. Jacobs S. C., Stephenson J. R., Wilkinson G. W. G. 1994; Protection elicited by a replication-defective adenovirus vector expressing the tick-borne encephalitis virus non-structural glycoprotein NS1. J Gen Virol 75:2399–2402 [CrossRef]
    [Google Scholar]
  17. Johnson A. J., Roehrig J. T. 1999; New mouse model for dengue virus vaccine testing. J Virol 73:783–786
    [Google Scholar]
  18. Konishi E., Pincus S., Fonseca B. A. L., Shope R. E., Paoletti E., Mason P. W. 1991; Comparison of protective immunity elicited by recombinant vaccinia viruses that synthesize E or NS1 of Japanese encephalitis virus. Virology 185:401–410 [CrossRef]
    [Google Scholar]
  19. Kurane I., Innis B. L., Nimmannitya S., Nisalak A., Meager A., Janus J., Ennis F. A. 1991; Activation of T lymphocytes in dengue virus infections: high levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon- γ in sera of children with dengue. J Clin Invest 88:1473–1480 [CrossRef]
    [Google Scholar]
  20. Lin Y.-L., Chen L.-K., Liao C.-L., Yeh C.-T., Ma S.-H., Chen J.-L., Huang Y.-L., Chen S.-S., Chiang H.-Y. 1998; DNA immunization with Japanese encephalitis virus nonstructural protein NS1 elicits protective immunity in mice. J Virol 72:191–200
    [Google Scholar]
  21. Littaua R., Kurane I., Ennis F. A. 1990; Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. J Immunol 144:3183–3186
    [Google Scholar]
  22. Lobigs M., Arthur C. E., Müllbacher A., Blanden R. V. 1994; The flavivirus nonstructural protein NS3 is a dominant source of cytotoxic T cell peptide determinants. Virology 202:195–201 [CrossRef]
    [Google Scholar]
  23. Monath T. P. 1994; Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A 91:2395–2400 [CrossRef]
    [Google Scholar]
  24. Muller U., Steinhoff U., Reis L. F., Hemmi S., Pavlovic J., Zinkernagel R. M., Aguet M. 1994; Functional role of type I and type II interferons in antiviral defense. Science 264:1918–1921 [CrossRef]
    [Google Scholar]
  25. Obijeski J. F., Bishop D. H. L., Murphy F. A., Palmer E. L. 1976; Structural proteins of La Crosse virus. J Virol 19:985–997
    [Google Scholar]
  26. Pletnev A. G., Bray M., Hanley K. A., Speicher J., Elkins R. 2001; Tick-borne langat/mosquito-borne dengue flavivirus chimera, a candidate live attenuated vaccine for protection against disease caused by members of the tick-borne encephalitis virus complex: evaluation in rhesus monkeys and in mosquitoes. J Virol 75:8259–8267 [CrossRef]
    [Google Scholar]
  27. Pletnev A. G., Claire M. S., Elkins R., Speicher J., Murphy B. R., Chanock R. M. 2003; Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus. Virology 314:190–195 [CrossRef]
    [Google Scholar]
  28. Pugachev K. V., Mason P. W., Shope R. E., Frey T. K. 1995; Double-subgenomic Sindbis virus recombinants expressing immunogenic proteins of Japanese encephalitis virus induce significant protection in mice against lethal JEV infection. Virology 212:587–594 [CrossRef]
    [Google Scholar]
  29. Qu X., Chen W., Maguire T., Austin F. 1993; Immunoreactivity and protective effects in mice of a recombinant dengue 2 Tonga virus NS1 protein produced in a baculovirus expression system. J Gen Virol 74:89–97 [CrossRef]
    [Google Scholar]
  30. Reed L. J., Muench H. 1938; A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497
    [Google Scholar]
  31. Roehrig J. T. 2003; Antigenic structure of flavivirus protein. Adv Virus Res 59:141–175
    [Google Scholar]
  32. Schlesinger J. J., Foltzer M., Chapman S. 1993; The Fc portion of antibody to yellow fever virus NS1 is a determinant of protection against YF encephalitis in mice. Virology 192:132–141 [CrossRef]
    [Google Scholar]
  33. Shresta S., Kyle J. L., Snider H. M., Basavapatna M., Beatty P. R., Harris E. 2004; Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical. J Virol 78:2701–2710 [CrossRef]
    [Google Scholar]
  34. Spaulding A., Kurane I., Ennis F. A., Rothman A. L. 1999; Analysis of murine CD8+ T-cell clones specific for the dengue virus NS3 protein: flavivirus cross-reactivity and influence of infecting serotype. J Virol 73:398–403
    [Google Scholar]
  35. van den Broek M. F., Muller U., Huang S., Aguet M., Zinkernagel R. M. 1995; Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. J Virol 69:4792–4796
    [Google Scholar]
  36. van der Most R. G., Murali-Krishna K., Ahmed R., Strauss J. H. 2000; Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response. J Virol 74:8094–8101 [CrossRef]
    [Google Scholar]
  37. Zhang Y.-M., Hayes E. P., McCarty T. C., Dubois D. R., Summers P. L., Eckels K. H., Chanock R. M., Lai C.-J. 1988; Immunization of mice with dengue structural proteins and nonstructural protein NS1 expressed by baculovirus recombinant induces resistance to dengue virus encephalitis. J Virol 62:3027–3031
    [Google Scholar]
  38. Zhao B. T., Prince G., Horswood R., Eckels K., Summers P., Chanock R., Lai C.-J. 1987; Expression of dengue virus structural proteins and nonstructural protein NS1 by a recombinant vaccinia virus. J Virol 61:4019–4022
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81256-0
Loading
/content/journal/jgv/10.1099/vir.0.81256-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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