1887

Abstract

Eleven clones of dengue virus 2 Mexican strain were selected by the size of their lytic plaques. Nucleotide sequences of the clones producing large plaques (D2ML2, D2ML3 and D2ML4) revealed 11 mutations, 10 of which were silent. The substitution at nucleotide 1168 (G → C) generates one amino acid difference at residue 390 (Asp → His) of the envelope protein (E). These clones showed high virulence in suckling mice when inoculated intracerebrally (⩾ 70% mortality). However, the clones which showed small lytic plaques (D2MS1, D2MS2 and D2MS4) displayed a substitution from Asp → Asn at the same positio nand had attenuated virulence. Based on these data, we suggest that substitution of Asp → His at residue 390 perhaps affects a functionally important structural element that could be a determinant of dengue neurovirulence. This substitution falls in domain III of the E protein, which plays an important role in viral binding; therefore, we propose that the substitution affects virulence and cellular tropism.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-10-2541
1996-10-01
2022-01-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/10/JV0770102541.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-10-2541&mimeType=html&fmt=ahah

References

  1. 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]
  2. Eckels K. H., Brandt W. E., Harrison V. R., McConn J. M., Rusell P. K. 1976; Isolation of a temperature-sensitive dengue 2 virus under conditions suitable for vaccine development. Infection and Immunity 14:1221–1227
    [Google Scholar]
  3. Hahn C. S., Darlymple J. M., Strauss J. H., Rice C. M. 1987; Comparison of the virulent Asibi strain of yellow fever virus with the 17D vaccine strain derived from it. Proceedings of the National Academy of Sciences, USA 84:2019–2023
    [Google Scholar]
  4. Halstead S. B. 1988; Pathogenesis of dengue; challenge to molecular biology. Science 239:476–481
    [Google Scholar]
  5. Harrison V. R., Eckels K. H., Sagartz J. W., Rusell P. K. 1977; Virulence and immunogenicity of a temperature-sensitive dengue 2 virus in lower primates. Infection and Immunity 18:151–156
    [Google Scholar]
  6. Hasegawa H., Yoshida M., Shiosaaka 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 191:158–165
    [Google Scholar]
  7. Holzmann H., Heinz F. X., Mandl C. W., Guirakhoo F., Funz C. 1990; A single amino acid substitution in envelope protein E of tick-borne encephalitis virus leads to attenuation in the mouse model. Journal of Virology 64:5156–5159
    [Google Scholar]
  8. Igarashi A. 1984; A hypothesis on the geographical distribution of arbovirus. Tropical Medicine 26:173–180
    [Google Scholar]
  9. Lobigs R., 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]
  10. MaeKawa S., Enomoto N., Kurosaki M., Maroma F., Sato C. 1995; Host dependent variation of hepatitis C virus; phylogenetic analyses. Archives of Virology 140:2123–2133
    [Google Scholar]
  11. Mandl C. W., Heinz F. X., Kunz C. 1988; Sequence of structural proteins of tick-borne encephalitis virus (Western subtype) and comparative analysis with other flaviviruses. Virology 166:197–205
    [Google Scholar]
  12. Monath T. P. 1986; Pathobiology of the flaviviruses. In The Togaviridae and Flaviviridae pp 375–440 Edited by Schlesinger S., Schlesinger M. J. New York: Plenum Press;
    [Google Scholar]
  13. Ng M. L., Lau C. L. 1988; Possible involvement of receptors in the entry of Kunjin virus into Vero cells. Archives of Virology 100:199–211
    [Google Scholar]
  14. Nitayaphan S., Grant J. A., Chang J. A., Chang G. J., Trent D. W. 1990; Nucleotide sequence of the virulent SA-14 strain of Japanese encephalitis virus and its attenuated vaccine derivative, SA-14-14-2. Virology 177:541–552
    [Google Scholar]
  15. Pletnev A. G., Bray M., Lai C.-J. 1993; Chimeric tick-borne encephalitis and dengue 4 viruses: effects of mutations on neurovirulence in mice. Journal of Virology 67:4956–4963
    [Google Scholar]
  16. Rey F. A., Heinz F. X., Mandl C., Kunz C., Harrison S. C. 1995; The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolution. Nature 375:291–298
    [Google Scholar]
  17. Rice C. M., Strauss E. G., Strauss J. H. 1986; Structure of the flavivirus genome. In Togaviridae and Flaviviridae pp 279–326 Edited by Schlesinger S., Schlesinger M. J. New York: Plenum Press;
    [Google Scholar]
  18. Rosen L. 1977; The emperor′s new clothes revisited, or reflections on the pathogenesis of dengue hemorragic fever. American Journal of Tropical Medicine and Hygiene 26:337–343
    [Google Scholar]
  19. Rusell D. L., Dalrymple J. M., Johnston R. E. 1989; Sindbis virus mutations which coordinately affect glycoprotein processing, penetration, and virulence in mice. Journal of Virology 63:1619–1629
    [Google Scholar]
  20. Shiodo T., Oka S., Ida S., Nokihara K., Toriyoshi H., Mori S., Takebe Y., Kimura S., Shimada K., Nagai Y. 1994; A naturally occurring single basic amino acid substitution in the V3 region of human immunodeficiency virus type 1. Env protein alters the cellular host range and antigenic structure of the virus. Journal of Virology 68:7689–7696
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-10-2541
Loading
/content/journal/jgv/10.1099/0022-1317-77-10-2541
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