1887

Abstract

Monoclonal antibodies (MAbs) specific for the E2c neutralizing antigenic site on the Sindbis virus E2 glycoprotein define a pathogenesis domain that affects neonatal mouse virulence. Sequence analysis of E2c MAb escape mutants showed that the domain included E2 amino acids 62, 96 and 159. The pathogenesis domain is also influenced by changes at E2 position 114. Mutation of E2 residues Asn 62 to Asp or Lys 159 to Glu results in suppression of the attenuated phenotype conferred by a mutation from Ser to Arg at E2 position 114. Possible mechanisms of phenotypic suppression within the E2c pathogenesis domain were investigated by using site-directed mutagenesis to determine the effects of specific combinations of positively charged, negatively charged and uncharged amino acid substitutions at E2 positions 62, 114 and 159. Phenotypic reversion to virulence by second-site suppressor mutations at E2 amino acids 62 or 159 was not dependent on ionic interaction with the residue at E2 114. Rather, suppression appeared to be the result of independent virulence effects mediated by specific residues.

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1993-08-01
2024-11-08
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References

  1. Baric R.S, Trent DW, Johnston RE. 1981; Sindbis virus variant with a cell-determined latent period.. Virology 110:237–242
    [Google Scholar]
  2. Dalrymple JM, Schlesinger S, Russell PK. 1976; Antigenic characterization of two Sindbis envelope glycoproteins separated by isoelectric focusing.. Virology 69:93–103
    [Google Scholar]
  3. Davis NL, Fuller FJ, Dougherty WG, Olmsted RA, Johnston RE. 1986; A single nucleotide change in the E2 glycoprotein gene of Sindbis virus affects penetration rate in cell culture and virulence in neonatal mice.. Proceedings of the National Academy of Sciences, U.S.A. 83:6771–6775
    [Google Scholar]
  4. Davis NL, Powell N, Greenwald GF, Willis L, Johnson BJB, Smith JF, Johnston RE. 1991; Attenuating mutations in the E2 glycoprotein gene of Venezuelan equine encephalitis virus: construction of single and multiple mutants in a full-length cDNA clone.. Virology 183:20–31
    [Google Scholar]
  5. Flynn DC, Olmsted RA, Mackenzie JM, Jr & Johnston RE. 1988; Antibody-mediated activation of Sindbis virus.. Virology 166:82–90
    [Google Scholar]
  6. Glasgow G.M, Sheahan BJ, Atkins GJ, Wahlberg JM, Salminen A, Liljestrom P. 1991; Two mutations in the envelope glycoprotein E2 of Semliki Forest virus affecting the maturation and entry patterns of the virus alter pathogenicity for mice.. Virology 185:741–748
    [Google Scholar]
  7. Kunkel TA, Roberts JD, Zakour RA. 1987; Rapid and efficient site-specific mutagenesis without phenotypic selection.. Methods in Enzymology 154:367–382
    [Google Scholar]
  8. Lustig S, Jackson AC, Hahn CS, Griffin DE, Strauss EG, Strauss JH. 1988; Molecular basis of Sindbis virus neurovirulence in mice.. Journal of Virology 62:2329–2336
    [Google Scholar]
  9. Olmsted RA, Baric RS, Sawyer BA, Johnston RE. 1984; Sindbis virus mutants selected for rapid growth in cell culture display attenuated virulence for animals.. Science 225:424–427
    [Google Scholar]
  10. Olmsted RA, Meyer WJ, Johnston RE. 1986; Characterization of Sindbis virus epitopes important for penetration in cell culture and pathogenesis in animals.. Virology 148:245–254
    [Google Scholar]
  11. Paredes AM, Simon MN, Brown DT. 1992; The mass of the Sindbis virus nucleocapsid suggests it has T = 4 icosahedral symmetry.. Virology 187:329–332
    [Google Scholar]
  12. Pence DF, Davis NL, Johnston RE. 1990; Antigenic and genetic characterization of Sindbis virus monoclonal antibody escape mutants which define a pathogenesis domain on glycoprotein E2.. Virology 175:41–49
    [Google Scholar]
  13. Polo JM, Johnston RE. 1990; Attenuating mutations in glycoproteins E1 and E2 of Sindbis virus produce a highly attenuated strain when combined in vitro.. Journal of Virology 64:4438–4444
    [Google Scholar]
  14. Polo JM, Johnston RE. 1991; Mutational analysis of a virulence locus in the E2 glycoprotein gene of Sindbis virus.. Journal of Virology 65:6358–6361
    [Google Scholar]
  15. Polo JM, Davis NL, Rice CM, Huang HV, Johnston RE. 1988; Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro.. Journal of Virology 62:2124–2133
    [Google Scholar]
  16. Rice CM, Strauss JH. 1982; Association of Sindbis virion glycoproteins and their precursors.. Journal of Molecular Biology 154:325–348
    [Google Scholar]
  17. Rice CM, Levis R, Strauss JH, Huang HV. 1987; Production of infectious RNA transcripts from Sindbis virus cDNA clones: mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants. Journal of Virology 61:3809–3819
    [Google Scholar]
  18. Russell DL, Dalrymple JM, Johnston RE. 1989; Sindbis virus mutations which coordinately affect glycoprotein processing, penetration, and virulence in mice.. Journal of Virology 63:1619–1629
    [Google Scholar]
  19. Schlesinger S, Schlesinger MJ. 1986 The Togaviridae and Flaviviridae. New York: Plenum Press.;
    [Google Scholar]
  20. Schlesinger MJ, Schlesinger S, Burge BW. 1972; Identification of a second glycoprotein in Sindbis virus.. Virology 47:539–541
    [Google Scholar]
  21. Schmaljohn AL, Kokubun KM, Cole GA. 1983; Protective monoclonal antibodies define maturational and pH-dependent changes in Sindbis virus El glycoproteins.. Virology 130:144–154
    [Google Scholar]
  22. Schoepp RJ, Johnston RE. 1992; Directed mutagenesis of a Sindbis virus pathogenesis site.. Virology 193:149–159
    [Google Scholar]
  23. Sefton BM, Wickus GG, Burge BW. 1978; Enzymatic iodination of Sindbis virus proteins.. Journal of Virology 11:730–735
    [Google Scholar]
  24. Stanley J, Cooper SJ, Griffin DE. 1985; Alphavirus neurovirulence: monoclonal antibodies discriminating wild-type from neuroadapted Sindbis virus.. Journal of Virology 56:110–119
    [Google Scholar]
  25. Strauss JH, Burge BW, Pfefferkorn ER, Darnell JE. 1969; Identification of the membrane protein and “core” protein of Sindbis virus.. Proceedings of the National Academy of Sciences, U.S.A. 59:533–537
    [Google Scholar]
  26. Tucker PC, Griffin DE. 1991; Mechanism of altered Sindbis virus neurovirulence associated with a single-amino-acid change in the E2 glycoprotein.. Journal of Virology 65:1551–1557
    [Google Scholar]
  27. Ubol S, Griffith DE. 1991; Identification of a putative alphavirus receptor on mouse neural cells.. Journal of Virology 65:6913–6921
    [Google Scholar]
  28. von Bonsdorff CH, Harrison SC. 1975; Sindbis virus glycoproteins form a regular icosahedral surface lattice.. Journal of Virology 16:141–145
    [Google Scholar]
  29. Vrati S, Faragher SG, Weir RC, Dalgarno L. 1986; Ross River virus mutant with a deletion in the E2 gene: properties of the virion, virus-specific macromolecule synthesis, and attenuation of virulence for mice.. Virology 151:222–232
    [Google Scholar]
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