1887

Abstract

Serial passage of yellow fever virus (YF17D) in mouse brain enhances neurovirulence, causing a reduction in survival time after intracerebral inoculation of adult mice. To study the biological and genetic basis for this phenomenon, we compared neurovirulence properties of the neuroadapted Porterfield strain (PYF) to a YF17D strain generated from a full-length YF cDNA template (YF5.2iv). Adult mice were infected by olfactory bulb inoculation, which results in widespread distribution of virus throughout the central nervous system. Although PYF and YF5.2iv spread rapidly throughout the neuraxis, maximal titres of PYF in the brain and spinal cord were 1000- to 10000-fold higher than those of YF5.2iv. Paralysis and death occurred earlier with the PYF strain. Several cDNA clones of the E/NS1 region of the PYF strain were sequenced. Three predicted amino acid changes were consistently observed in the envelope protein of the PYF strain compared to YF5.2iv. Common substitutions were also identified in NS1 and NS2A. The potential contribution of these genetic differences to neurovirulence was evaluated by generating recombinant, intertypic PYF/YF5.2iv viruses. Physical signs of disease and mean spinal cord titres after inoculation of one recombinant were not different from the YF5.2iv parent. Our data indicate that PYF and YF5.2iv differ significantly in their virulence properties, however, common amino acid substitutions in the E/NS1 region of the PYF strain do not determine its enhanced neurovirulence. Other regions of the viral genome may contribute dominant effects on the virulence properties of the PYF strain.

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1996-06-01
2022-05-28
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References

  1. Agol V. I., Dzrozdovb S. G., Grachev V. P., Kolesnikova M. S., Kozlov V. G., Ralph N. M., Romanova L. I., Tolskaya E. A., Tyufanov A. V., Viktorova E. G. 1985; Recombinants between attenuated and virulent strains of poliovirus type 1: derivation and characterization of recombinants with centrally located crossover points. Virology 143:467–477
    [Google Scholar]
  2. Barrett A. D. T., Monath T. P., Cropp C. P., Adkins J. D., Ledger T. N., Gould E. A., Schlesinger J. J., Kinney R. M., Trent D. W. 1990; Attenuation of wild-type yellow fever virus by passage in HeLa cells. Journal of General Virology 71:2301–2306
    [Google Scholar]
  3. Blok J., McWilliam S. M., Butler H. C., Gibbs A. J., Weiller G., Herring B. L., Hemsley A. C., Aaskov J. G., Yoksan S., Bhamarapravati N. 1992; Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses. Virology 187:573–590
    [Google Scholar]
  4. Brandriss M. W., Schlesinger J. J., Walsh E. E., Briselli M. 1986; Lethal 17D yellow fever encephalitis in mice I. Passive protection by monoclonal antibodies to the envelope proteins of 17D yellow fever and dengue 2 viruses. Journal of General Virology 67:229–234
    [Google Scholar]
  5. Bray M., Lai C. J. 1991; Construction of intertypic chimeric dengue viruses by substitution of structural proteins. Proceedings of the National Academy of Sciences, USA 88:10342–10346
    [Google Scholar]
  6. Bray M., Zhao B. T., Markoff L., Eckels K. H., Chanock R. M., Lai C. J. 1989; Mice immunized with recombinant vaccinia virus expressing dengue virus 4 structural proteins with or without NS1 are protected against fatal dengue virus encephalitis. Journal of Virology 63:2853–2856
    [Google Scholar]
  7. Cane P. A., Gould E. A. 1989; Immunoblotting reveals differences in the accumulation of envelope protein by wild-type and vaccine strains of yellow fever virus. Journal of General Virology 70:557–564
    [Google Scholar]
  8. Carp R. I, Davidson A. I., Merz P. A. 1971; A method for obtaining cerebrospinal fluid from mice. Research in Veterinary Science 12:499
    [Google Scholar]
  9. Cecilia D., Gould E. A. 1991; Nucleotide changes responsible for loss of neuroinvasiveness in Japanese encephalitis virus neutralization-resistant mutants. Virology 181:70–77
    [Google Scholar]
  10. Chambers T. J., McCourt D. W., Rice C. M. 1989; Yellow fever virus proteins NS2A, NS2B, and NS4B: identification and partial N-terminal amino acid sequence analysis. Virology 169:100–109
    [Google Scholar]
  11. Chambers T. J., Hahn C. S., Galler R., Rice C. M. 1990; Flavivirus genome organization, expression and replication. Annual Review of Microbiology 44:649–688
    [Google Scholar]
  12. Converse J. L., Kovatch R. M., Pulliam J. D., Nagle S. C. Jr, Snyder E. M. 1971; Virulence and pathogenesis of yellow fever virus serially passaged in cell culture. Applied Microbiologv 21:1053–1057
    [Google Scholar]
  13. Findlay G. M., Clark L. P. 1935; Infection with neurotropic yellow fever virus following instillation into the nares and conjunctival sac. Journal of Pathology and Bacteriology 40:55–64
    [Google Scholar]
  14. Gould E. A., Buckley A., Barrett A. D. T., Cammack N. 1986; Neutralizing (54K) and non-neutralizing (54K and 48K) monoclonal antibodies against structural and non–structural yellow fever virus proteins confer immunity in mice. Journal of General Virology 67:591–595
    [Google Scholar]
  15. Gritsun T. S., Holmes E. C., Gould E. A. 1995; Analysis of flavivirus envelope proteins reveals variable domains that reflect their antigenicity and may determine their pathogenesis. Virus Research 35:307–321
    [Google Scholar]
  16. Hahn C. S., Dalrymple J. M., Strauss J. H., Rice C. M. 1987; Comparison of the virulent Asibi strain of yellow fever virus with the 17D vaccine derived from it. Proceedings of the National Academy of Sciences, USA 84:2019–2023
    [Google Scholar]
  17. Hardy F. M. 1963; The growth of Asibi strain yellow fever virus in tissue cultures. II. Modification of virus and cells. Journal of Infectious Diseases 113:9–14
    [Google Scholar]
  18. Hearn H. J. Jr, Soper W. T., Miller W. S. 1965; Loss in virulence of yellow fever virus serially passed in HeLa cells. Proceedings of the Society for Experimental Biology and Medicine 119:319–322
    [Google Scholar]
  19. Hearn H. J. Jr, Chappell W. A., Demchak P., Dominik J. W. 1966; Attenuation of aerosolized yellow fever virus after passage in cell culture. Bacteriological Reviews 30:615–625
    [Google Scholar]
  20. Hasegawa H., Yoshida M., Shiosaka T., Fujita S., Kobayashi Y. 1992; Mutations in the envelope protein of Japanese encephalitis virus affect entry into cultured cells and virulence in mice. Virology 191:158–65
    [Google Scholar]
  21. Hirsch M. S., Murphy F. A. 1967; Effects of anti-thymocyte serum on 17-D yellow fever infection in adult mice. Nature 216:179–180
    [Google Scholar]
  22. Holzmann H., Heinz F. X., Mandl C. M., Guirakhoo F., Kunz C. 1990; A single amino acid substitution in the envelope protein E of tick-borne encephalitis virus leads to attenuation in the mouse model. Journal of Virology 64:5156–5159
    [Google Scholar]
  23. Jennings A. D., Whitby J. E., Minor P. D., Barrett A. D. T. 1993; Nucleotide and deduced amino acid sequence of the envelope protein of the wild-type French viscerotropic strain of yellow fever virus and the French neurotropic vaccine strain derived from it. Virology 192:692–695
    [Google Scholar]
  24. Jennings A. D., Gibson C. A., Miller B. R., Mathews J. H., Mitchell C. J., Roehrig J. T., Wood D. J., Taffs F., Sil B. K., Whitby S. N., Whitby J. E., Monath T. P., Minor P. D., Sanders P. G., Barrett A. D. T. 1994; Analysis of a yellow fever virus isolated from a fatal case of vaccine-associated encephalitis. Journal of Infectious Diseases 169:512–518
    [Google Scholar]
  25. Jiang W. R., Lowe A., Higgs S., Reid H., Gould E. A. 1993; Single amino acid codon changes detected in louping ill virus antibody-resistant mutants with reduced virulence. Journal of General Virology 74:931–935
    [Google Scholar]
  26. Kawano H., Rostapshov V., Rosen L., Lai C.-J. 1993; Genetic determinants of dengue type 4 virus neurovirulence for mice. Journal of Virology 67:6567–6575
    [Google Scholar]
  27. 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
    [Google Scholar]
  28. Lin C., Amberg S. M., Chambers T. J., Rice C. M. 1993; Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site. Journal of Virology 67:2327–2335
    [Google Scholar]
  29. Lobigs M., Usha R., Nestorowicz A., Marshall I. D., Weir R. C., Dalgarno L. 1990; Host cell selection of Murray Valley encephalitis virus variants altered at an RGD sequence in the envelope protein and in mouse virulence. Virology 176:587–595
    [Google Scholar]
  30. McMinn P. C., Marshall I. D., Dalgarno L. 1995a; Neurovirulence and neuroinvasiveness of Murray Valley encephalitis virus mutants selected by passage in a monkey kidney cell line. Journal of General Virology 76:865–872
    [Google Scholar]
  31. McMinn P. C., Lee E., Hartley S., Roehrig J. T., Dalgarno L., Weir R. C. 1995b; Murray Valley encephalitis virus envelope protein antigenic variants with altered hemagglutination properties and reduced neuroinvasiveness in mice. Virology 211:10–20
    [Google Scholar]
  32. Meers P. D. 1959; Adaptation of the 17D yellow fever virus to mouse brain by serial passage. Transactions of the Royal Society of Tropical Medicine and Hygiene 53:445–457
    [Google Scholar]
  33. Monath T. P., Cropp C. B., Harrison A. K. 1983; Mode of entry of a neurotropic arbovirus into the central nervous system: Reinvestigation of an old controversy. Laboratory Investigation 48:399–410
    [Google Scholar]
  34. Nitayaphan S., Grant J. A., Chang G.-J. J., Trent D. W. 1990; Nucleotide sequence of the virulent SA–14 strain of Japanese encephalitis virus and its attenuated vaccine derivative, SA14–14–2. Virology 177:541–552
    [Google Scholar]
  35. Ogata A., Nagashima K., Hall W. H., Ichikawa M., Kimura-Kuroda J., Yasui K. 1991; Japanese encephalitis virus neurotropism is dependent on the degree of neuronal maturity. Journal of Virology 65:880–886
    [Google Scholar]
  36. Omata T., Kohara M., Kuge S., Komatsu T., Abe S., Semler B. L., Kameda A., Itoh H., Arita M., Wimmer E., Nomoto A. 1986; Genetic analysis of the attenuation phenotype of poliovirus type 1. Journal of Virology 58:348–358
    [Google Scholar]
  37. Pletnev A. G., Bray M., Lai C.-J. 1993; Chimeric tick-borne encephalitis and dengue type 4 viruses: effects of mutations on neurovirulence in mice. Journal of Virology 67:4956–4963
    [Google Scholar]
  38. Rey F. A., Heinz F. X., Mandl C., Kunz C., Harrison S. 1995; The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375:291–298
    [Google Scholar]
  39. Rice C. M., Lenches E. M., Eddy S. R., Shin S. J., Sheets R. L., Strauss J. H. 1985; Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 229:726–733
    [Google Scholar]
  40. Rice C. M., Strauss E. G., Strauss J. H. 1986; Structure of the flavivirus genome. In The Togaviridae and Flaviviridae pp. 279–326 Edited by Schlessinger S., Schlessinger M. J. New York: Plenum Press;
    [Google Scholar]
  41. Rice C. M., Grakoui A., Galler R., Chambers T. J. 1989; Transcription of infectious yellow fever virus RNA from full-length cDNA templates produced by in vitro ligation. New Biologist 1:285–296
    [Google Scholar]
  42. Sabin A. B. 1952; Nature of inherited resistance to viruses affecting the nervous system. Proceedings of the National Academy of Sciences, USA 38:540–546
    [Google Scholar]
  43. Schlesinger R. W. 1980; Virus-host interactions in natural and experimental infections with alphaviruses and flaviviruses. In The Togaviruses pp. 83–104 Edited by Schlesinger R. W. New York & London: Academic Press;
    [Google Scholar]
  44. Schlesinger J. J., Brandriss M. W., Walsh E. E. 1985; Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the non-structural glycoprotein gp48 and by active immunization with gp48. Journal of Immunology 135:2805–2809
    [Google Scholar]
  45. Schlesinger J. J., Brandriss M. W., Cropp C. B., Monath T. P. 1986; Protection against yellow fever in monkeys by immunization with yellow fever virus nonstructural protein NS1. Journal of Virology 60:1153–1155
    [Google Scholar]
  46. Schlesinger J. J., Brandriss M. W., Putnak J. R., Walsh E. E. 1990; Cell surface expression of yellow fever virus nonstructural glycoprotein NS1: consequences of interaction with antibody. Journal of General Virology 71:593–599
    [Google Scholar]
  47. Sumiyoshi H., Tignor G. H., Shope R. E. 1995; Characterization of a highly attenuated Japanese encephalitis virus generated from molecularly cloned cDNA. Journal of Infectious Diseases 171:1144–1151
    [Google Scholar]
  48. Tardy-Panit M., Blondel B., Martin A., Tekaia F., Horaud F., Delpeyroux F. 1993; A mutation in the RNA polymerase of poliovirus type 1 contributes to attenuation in mice. Journal of Virology 67:4630–4638
    [Google Scholar]
  49. Theiler M. 1951; The virus. In Yellow Fever pp. 46–136 Edited by Strode G. K. New York: McGraw-Hill;
    [Google Scholar]
  50. Zar J. H. 1974; Nonparametric tests. In Biostatistical Analysis pp. 151–162 New Jersey: Prentice-Hall;
    [Google Scholar]
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