Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Jan;80(1):70–74. doi: 10.1073/pnas.80.1.70

Characterization of an antigenic determinant of the glycoprotein that correlates with pathogenicity of rabies virus.

B Dietzschold, W H Wunner, T J Wiktor, A D Lopes, M Lafon, C L Smith, H Koprowski
PMCID: PMC393311  PMID: 6185960

Abstract

The pathogenicity of fixed rabies virus strains for adult mice depends on the presence of an antigenic determinant on the viral glycoprotein. Two virus-neutralizing monoclonal antibodies have been used to identify this determinant. All pathogenic strains of fixed rabies virus bind to these antibodies and are neutralized by them, whereas nonpathogenic strains fail to react with these monoclonal antibodies and are not neutralized by them. Antigenic variants of the rabies virus with altered glycoprotein were selected by growing virus in the presence of one monoclonal antibody, 194-2. All variants that lost their ability to react with this antibody and an additional antibody, 248-8, were found to be nonpathogenic for adult mice. Analysis of tryptic peptides of the glycoproteins of pathogenic parent virus and nonpathogenic variants and the amino acid sequence of a specific variant tryptic peptide revealed that the change in pathogenicity corresponded to an amino acid substitution at position 333 of the glycoprotein molecule. The nucleotide sequence of the nonpathogenic variant glycoprotein gene contained a base change that confirmed the single amino acid substitution in the tryptic peptide replacing arginine-333 in the parental glycoprotein. We conclude that arginine-333 is essential for the integrity of an antigenic determinant and for the ability of rabies viruses to produce lethal infection in adult mice.

Full text

PDF
70

Images in this article

74Image
on p.74
74Image
on p.74

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anilionis A., Wunner W. H., Curtis P. J. Structure of the glycoprotein gene in rabies virus. Nature. 1981 Nov 19;294(5838):275–278. doi: 10.1038/294275a0. [DOI] [PubMed] [Google Scholar]
  2. Bosch F. X., Orlich M., Klenk H. D., Rott R. The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses. Virology. 1979 May;95(1):197–207. doi: 10.1016/0042-6822(79)90414-8. [DOI] [PubMed] [Google Scholar]
  3. Both G. W., Air G. M. Nucleotide sequence coding for the N-terminal region of the matrix protein influenza virus. Eur J Biochem. 1979 May 15;96(2):363–372. doi: 10.1111/j.1432-1033.1979.tb13048.x. [DOI] [PubMed] [Google Scholar]
  4. Clark H. F., Parks N. F., Wunner W. H. Defective interfering particles of fixed rabies viruses: lack of correlation with attenuation or auto-interference in mice. J Gen Virol. 1981 Feb;52(Pt 2):245–258. doi: 10.1099/0022-1317-52-2-245. [DOI] [PubMed] [Google Scholar]
  5. Clark H. F. Rabies viruses increase in virulence when propagated in neuroblastoma cell culture. Science. 1978 Mar 10;199(4333):1072–1075. doi: 10.1126/science.628831. [DOI] [PubMed] [Google Scholar]
  6. Coulon P., Rollin P., Aubert M., Flamand A. Molecular basis of rabies virus virulence. I. Selection of avirulent mutants of the CVS strain with anti-G monoclonal antibodies. J Gen Virol. 1982 Jul;61(Pt 50):97–100. doi: 10.1099/0022-1317-61-1-97. [DOI] [PubMed] [Google Scholar]
  7. Flamand A., Wiktor T. J., Koprowski H. Use of hybridoma monoclonal antibodies in the detection of antigenic differences between rabies and rabies-related virus proteins. II. The glycoprotein. J Gen Virol. 1980 May;48(1):105–109. doi: 10.1099/0022-1317-48-1-105. [DOI] [PubMed] [Google Scholar]
  8. KOPROWSKI H., BLACK J., NELSEN D. J. Studies on chick-embryo-adapted-rabies virus. VI. Further changes in pathogenic properties following prolonged cultivation in the developing chick embryo. J Immunol. 1954 Jan;72(1):94–106. [PubMed] [Google Scholar]
  9. Kilbourne E. D. Genetic dimorphism in influenza viruses: characterization of stably associated hemagglutinin mutants differing in antigenicity and biological properties. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6258–6262. doi: 10.1073/pnas.75.12.6258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  11. Nagai Y., Klenk H. D., Rott R. Proteolytic cleavage of the viral glycoproteins and its significance for the virulence of Newcastle disease virus. Virology. 1976 Jul 15;72(2):494–508. doi: 10.1016/0042-6822(76)90178-1. [DOI] [PubMed] [Google Scholar]
  12. Rott R. Molecular basis of infectivity and pathogenicity of myxovirus. Brief review. Arch Virol. 1979;59(4):285–298. doi: 10.1007/BF01317469. [DOI] [PubMed] [Google Scholar]
  13. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sleigh M. J., Both G. W., Underwood P. A., Bender V. J. Antigenic drift in the hemagglutinin of the Hong Kong influenza subtype: correlation of amino acid changes with alterations in viral antigenicity. J Virol. 1981 Mar;37(3):845–853. doi: 10.1128/jvi.37.3.845-853.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Spriggs D. R., Fields B. N. Attenuated reovirus type 3 strains generated by selection of haemagglutinin antigenic variants. Nature. 1982 May 6;297(5861):68–70. doi: 10.1038/297068a0. [DOI] [PubMed] [Google Scholar]
  16. Sweet C., Smith H. Pathogenicity of influenza virus. Microbiol Rev. 1980 Jun;44(2):303–330. doi: 10.1128/mr.44.2.303-330.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Vaheri A., Sedwick W. D., Plotkin S. A., Maes R. Cytopathic effect of rubella virus in RHK21 cells and growth to high titers in suspension culture. Virology. 1965 Oct;27(2):239–241. doi: 10.1016/0042-6822(65)90170-4. [DOI] [PubMed] [Google Scholar]
  18. Weiner H. L., Drayna D., Averill D. R., Jr, Fields B. N. Molecular basis of reovirus virulence: role of the S1 gene. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5744–5748. doi: 10.1073/pnas.74.12.5744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wiktor T. J., Dietzschold B., Leamnson R. N., Koprowski H. Induction and biological properties of defective interfering particles of rabies virus. J Virol. 1977 Feb;21(2):626–635. doi: 10.1128/jvi.21.2.626-635.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wiktor T. J., Koprowski H. Antigenic variants of rabies virus. J Exp Med. 1980 Jul 1;152(1):99–112. doi: 10.1084/jem.152.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wiktor T. J., Koprowski H. Monoclonal antibodies against rabies virus produced by somatic cell hybridization: detection of antigenic variants. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3938–3942. doi: 10.1073/pnas.75.8.3938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wunner W. H., Clark H. F. Regeneration of DI particles of virulent and attenuated rabies virus: genome characterization and lack of correlation with virulence phenotype. J Gen Virol. 1980 Nov;51(Pt 1):69–81. doi: 10.1099/0022-1317-51-1-69. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES