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. 1990 Oct;64(10):5156–5159. doi: 10.1128/jvi.64.10.5156-5159.1990

A single amino acid substitution in envelope protein E of tick-borne encephalitis virus leads to attenuation in the mouse model.

H Holzmann 1, F X Heinz 1, C W Mandl 1, F Guirakhoo 1, C Kunz 1
PMCID: PMC248008  PMID: 2398538

Abstract

We have determined the virulence characteristics of seven monoclonal antibody escape mutants of tick-borne encephalitis virus in the mouse model. One of the mutants with an amino acid substitution from tyrosine to histidine at residue 384 revealed strongly reduced pathogenicity after peripheral inoculation of adult mice but retained its capacity to replicate in the mice and to induce a high-titered antibody response. Infection with the attenuated mutant resulted in resistance to challenge with virulent virus. Assessment of nonconservative amino acid substitutions in other attenuated flaviviruses suggests that a structural element including residue 384 may represent an important determinant of flavivirus virulence in general.

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Selected References

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  1. Dalgarno L., Trent D. W., Strauss J. H., Rice C. M. Partial nucleotide sequence of the Murray Valley encephalitis virus genome. Comparison of the encoded polypeptides with yellow fever virus structural and non-structural proteins. J Mol Biol. 1986 Feb 5;187(3):309–323. doi: 10.1016/0022-2836(86)90435-3. [DOI] [PubMed] [Google Scholar]
  2. Deubel V., Kinney R. M., Trent D. W. Nucleotide sequence and deduced amino acid sequence of the structural proteins of dengue type 2 virus, Jamaica genotype. Virology. 1986 Dec;155(2):365–377. doi: 10.1016/0042-6822(86)90200-x. [DOI] [PubMed] [Google Scholar]
  3. Fox G., Parry N. R., Barnett P. V., McGinn B., Rowlands D. J., Brown F. The cell attachment site on foot-and-mouth disease virus includes the amino acid sequence RGD (arginine-glycine-aspartic acid). J Gen Virol. 1989 Mar;70(Pt 3):625–637. doi: 10.1099/0022-1317-70-3-625. [DOI] [PubMed] [Google Scholar]
  4. Guirakhoo F., Heinz F. X., Kunz C. Epitope model of tick-borne encephalitis virus envelope glycoprotein E: analysis of structural properties, role of carbohydrate side chain, and conformational changes occurring at acidic pH. Virology. 1989 Mar;169(1):90–99. doi: 10.1016/0042-6822(89)90044-5. [DOI] [PubMed] [Google Scholar]
  5. Hahn C. S., Dalrymple J. M., Strauss J. H., Rice C. M. Comparison of the virulent Asibi strain of yellow fever virus with the 17D vaccine strain derived from it. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2019–2023. doi: 10.1073/pnas.84.7.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hahn Y. S., Galler R., Hunkapiller T., Dalrymple J. M., Strauss J. H., Strauss E. G. Nucleotide sequence of dengue 2 RNA and comparison of the encoded proteins with those of other flaviviruses. Virology. 1988 Jan;162(1):167–180. doi: 10.1016/0042-6822(88)90406-0. [DOI] [PubMed] [Google Scholar]
  7. Heinz F. X., Berger R., Tuma W., Kunz C. A topological and functional model of epitopes on the structural glycoprotein of tick-borne encephalitis virus defined by monoclonal antibodies. Virology. 1983 Apr 30;126(2):525–537. doi: 10.1016/s0042-6822(83)80010-5. [DOI] [PubMed] [Google Scholar]
  8. Heinz F. X., Berger R., Tuma W., Kunz C. Location of immunodominant antigenic determinants on fragments of the tick-borne encephalitis virus glycoprotein: evidence for two different mechanisms by which antibodies mediate neutralization and hemagglutination inhibition. Virology. 1983 Oct 30;130(2):485–501. doi: 10.1016/0042-6822(83)90102-2. [DOI] [PubMed] [Google Scholar]
  9. Heinz F. X., Tuma W., Guirakhoo F., Kunz C. A model study of the use of monoclonal antibodies in capture enzyme immunoassays for antigen quantification exploiting the epitope map of tick-borne encephalitis virus. J Biol Stand. 1986 Apr;14(2):133–141. doi: 10.1016/0092-1157(86)90032-6. [DOI] [PubMed] [Google Scholar]
  10. Holzmann H., Mandl C. W., Guirakhoo F., Heinz F. X., Kunz C. Characterization of antigenic variants of tick-borne encephalitis virus selected with neutralizing monoclonal antibodies. J Gen Virol. 1989 Jan;70(Pt 1):219–222. doi: 10.1099/0022-1317-70-1-219. [DOI] [PubMed] [Google Scholar]
  11. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  12. Kimura T., Gollins S. W., Porterfield J. S. The effect of pH on the early interaction of West Nile virus with P388D1 cells. J Gen Virol. 1986 Nov;67(Pt 11):2423–2433. doi: 10.1099/0022-1317-67-11-2423. [DOI] [PubMed] [Google Scholar]
  13. Lobigs M., Usha R., Nestorowicz A., Marshall I. D., Weir R. C., Dalgarno L. Host cell selection of Murray Valley encephalitis virus variants altered at an RGD sequence in the envelope protein and in mouse virulence. Virology. 1990 Jun;176(2):587–595. doi: 10.1016/0042-6822(90)90029-q. [DOI] [PubMed] [Google Scholar]
  14. Mandl C. W., Guirakhoo F., Holzmann H., Heinz F. X., Kunz C. Antigenic structure of the flavivirus envelope protein E at the molecular level, using tick-borne encephalitis virus as a model. J Virol. 1989 Feb;63(2):564–571. doi: 10.1128/jvi.63.2.564-571.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mandl C. W., Heinz F. X., Kunz C. Sequence of the structural proteins of tick-borne encephalitis virus (western subtype) and comparative analysis with other flaviviruses. Virology. 1988 Sep;166(1):197–205. doi: 10.1016/0042-6822(88)90161-4. [DOI] [PubMed] [Google Scholar]
  16. Mandl C. W., Heinz F. X., Stöckl E., Kunz C. Genome sequence of tick-borne encephalitis virus (Western subtype) and comparative analysis of nonstructural proteins with other flaviviruses. Virology. 1989 Nov;173(1):291–301. doi: 10.1016/0042-6822(89)90246-8. [DOI] [PubMed] [Google Scholar]
  17. Mason P. W., McAda P. C., Mason T. L., Fournier M. J. Sequence of the dengue-1 virus genome in the region encoding the three structural proteins and the major nonstructural protein NS1. Virology. 1987 Nov;161(1):262–267. doi: 10.1016/0042-6822(87)90196-6. [DOI] [PubMed] [Google Scholar]
  18. Nowak T., Wengler G. Analysis of disulfides present in the membrane proteins of the West Nile flavivirus. Virology. 1987 Jan;156(1):127–137. doi: 10.1016/0042-6822(87)90443-0. [DOI] [PubMed] [Google Scholar]
  19. Pletnev A. G., Yamshchikov V. F., Blinov V. M. Nucleotide sequence of the genome and complete amino acid sequence of the polyprotein of tick-borne encephalitis virus. Virology. 1990 Jan;174(1):250–263. doi: 10.1016/0042-6822(90)90073-z. [DOI] [PubMed] [Google Scholar]
  20. Pletnev A. G., Yamshchikov V. F., Blinov V. M. Tick-borne encephalitis virus genome. The nucleotide sequence coding for virion structural proteins. FEBS Lett. 1986 May 12;200(2):317–321. doi: 10.1016/0014-5793(86)81160-7. [DOI] [PubMed] [Google Scholar]
  21. Rice C. M., Grakoui A., Galler R., Chambers T. J. Transcription of infectious yellow fever RNA from full-length cDNA templates produced by in vitro ligation. New Biol. 1989 Dec;1(3):285–296. [PubMed] [Google Scholar]
  22. Rice C. M., Lenches E. M., Eddy S. R., Shin S. J., Sheets R. L., Strauss J. H. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science. 1985 Aug 23;229(4715):726–733. doi: 10.1126/science.4023707. [DOI] [PubMed] [Google Scholar]
  23. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  24. Sumiyoshi H., Morita K., Mori C., Fuke I., Shiba T., Sakaki Y., Igarashi A. Sequence of 3000 nucleotides at the 5' end of Japanese encephalitis virus RNA. Gene. 1986;48(2-3):195–201. doi: 10.1016/0378-1119(86)90077-6. [DOI] [PubMed] [Google Scholar]
  25. Trent D. W., Kinney R. M., Johnson B. J., Vorndam A. V., Grant J. A., Deubel V., Rice C. M., Hahn C. Partial nucleotide sequence of St. Louis encephalitis virus RNA: structural proteins, NS1, ns2a, and ns2b. Virology. 1987 Feb;156(2):293–304. doi: 10.1016/0042-6822(87)90409-0. [DOI] [PubMed] [Google Scholar]
  26. Wengler G., Castle E., Leidner U., Nowak T., Wengler G. Sequence analysis of the membrane protein V3 of the flavivirus West Nile virus and of its gene. Virology. 1985 Dec;147(2):264–274. doi: 10.1016/0042-6822(85)90129-1. [DOI] [PubMed] [Google Scholar]
  27. Winkler G., Heinz F. X., Kunz C. Characterization of a disulphide bridge-stabilized antigenic domain of tick-borne encephalitis virus structural glycoprotein. J Gen Virol. 1987 Aug;68(Pt 8):2239–2244. doi: 10.1099/0022-1317-68-8-2239. [DOI] [PubMed] [Google Scholar]
  28. Zhao B., Mackow E., Buckler-White A., Markoff L., Chanock R. M., Lai C. J., Makino Y. Cloning full-length dengue type 4 viral DNA sequences: analysis of genes coding for structural proteins. Virology. 1986 Nov;155(1):77–88. doi: 10.1016/0042-6822(86)90169-8. [DOI] [PubMed] [Google Scholar]

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