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. 1991 Mar;65(3):1551–1557. doi: 10.1128/jvi.65.3.1551-1557.1991

Mechanism of altered Sindbis virus neurovirulence associated with a single-amino-acid change in the E2 Glycoprotein.

P C Tucker 1, D E Griffin 1
PMCID: PMC239937  PMID: 1995953

Abstract

The mechanism by which amino acid changes in the E1 and E2 surface glycoproteins of Sindbis virus affect neurovirulence is unknown. We have studied two recombinant viruses which differ in virulence. One (TE) contains Gly and the other (TES) contains Arg at position 172 in E2. TE causes more rapid death than TES in newborn mice. Both viruses replicate similarly in nonneuronal cells, but TE replicates more rapidly in the brains of newborn mice and in neuroblastoma cells. TE also induces earlier viral RNA synthesis in neuroblastoma cells. 35S-labeled TE binds more efficiently to brain and neuroblastoma cells, but not to nonneuronal cells, than TES. We propose that a region of the E2 glycoprotein affected by the amino acid occupying position 172 is important for binding to an alphavirus receptor on neurons and influences neurovirulence by this mechanism.

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Selected References

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

  1. Amano T., Richelson E., Nirenberg M. Neurotransmitter synthesis by neuroblastoma clones (neuroblast differentiation-cell culture-choline acetyltransferase-acetylcholinesterase-tyrosine hydroxylase-axons-dendrites). Proc Natl Acad Sci U S A. 1972 Jan;69(1):258–263. doi: 10.1073/pnas.69.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bracha M., Schlesinger M. J. Defects in RNA+ temperature-sensitive mutants of Sindbis virus and evidence for a complex of PE2-E1 viral glycoproteins. Virology. 1976 Oct 15;74(2):441–449. doi: 10.1016/0042-6822(76)90350-0. [DOI] [PubMed] [Google Scholar]
  3. Burge B. W., Pfefferkorn E. R. Isolation and characterization of conditional-lethal mutants of Sindbis virus. Virology. 1966 Oct;30(2):204–213. doi: 10.1016/0042-6822(66)90096-1. [DOI] [PubMed] [Google Scholar]
  4. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  5. Davis N. L., Fuller F. J., Dougherty W. G., Olmsted R. A., Johnston R. E. A single nucleotide change in the E2 glycoprotein gene of Sindbis virus affects penetration rate in cell culture and virulence in neonatal mice. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6771–6775. doi: 10.1073/pnas.83.18.6771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davis N. L., Pence D. F., Meyer W. J., Schmaljohn A. L., Johnston R. E. Alternative forms of a strain-specific neutralizing antigenic site on the Sindbis virus E2 glycoprotein. Virology. 1987 Nov;161(1):101–108. doi: 10.1016/0042-6822(87)90175-9. [DOI] [PubMed] [Google Scholar]
  7. Doherty R. L. Arthropod-borne viruses in Australia, 1973-1976. Aust J Exp Biol Med Sci. 1977 Apr;55(2):103–130. doi: 10.1038/icb.1977.9. [DOI] [PubMed] [Google Scholar]
  8. Fries E., Helenius A. Binding of Semliki Forest virus and its spike glycoproteins to cells. Eur J Biochem. 1979 Jun;97(1):213–220. doi: 10.1111/j.1432-1033.1979.tb13105.x. [DOI] [PubMed] [Google Scholar]
  9. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  10. Griffin D. E., Johnson R. T. Role of the immune response in recovery from Sindbis virus encephalitis in mice. J Immunol. 1977 Mar;118(3):1070–1075. [PubMed] [Google Scholar]
  11. Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  12. JOHNSON R. T. VIRUS INVASION OF THE CENTRAL NERVOUS SYSTEM: A STUDY OF SINDBIS VIRUS INFECTION IN THE MOUSE USING FLUORESCENT ANTIBODY. Am J Pathol. 1965 Jun;46:929–943. [PMC free article] [PubMed] [Google Scholar]
  13. Jackson A. C., Moench T. R., Griffin D. E., Johnson R. T. The pathogenesis of spinal cord involvement in the encephalomyelitis of mice caused by neuroadapted Sindbis virus infection. Lab Invest. 1987 Apr;56(4):418–423. [PubMed] [Google Scholar]
  14. Jackson A. C., Moench T. R., Trapp B. D., Griffin D. E. Basis of neurovirulence in Sindbis virus encephalomyelitis of mice. Lab Invest. 1988 May;58(5):503–509. [PubMed] [Google Scholar]
  15. Johnson R. T., McFarland H. F., Levy S. E. Age-dependent resistance to viral encephalitis: studies of infections due to Sindbis virus in mice. J Infect Dis. 1972 Mar;125(3):257–262. doi: 10.1093/infdis/125.3.257. [DOI] [PubMed] [Google Scholar]
  16. Jones K. J., Scupham R. K., Pfeil J. A., Wan K., Sagik B. P., Bose H. R. Interaction of Sindbis virus glycoproteins during morphogenesis. J Virol. 1977 Feb;21(2):778–787. doi: 10.1128/jvi.21.2.778-787.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Luo M., Vriend G., Kamer G., Minor I., Arnold E., Rossmann M. G., Boege U., Scraba D. G., Duke G. M., Palmenberg A. C. The atomic structure of Mengo virus at 3.0 A resolution. Science. 1987 Jan 9;235(4785):182–191. doi: 10.1126/science.3026048. [DOI] [PubMed] [Google Scholar]
  18. Lustig S., Jackson A. C., Hahn C. S., Griffin D. E., Strauss E. G., Strauss J. H. Molecular basis of Sindbis virus neurovirulence in mice. J Virol. 1988 Jul;62(7):2329–2336. doi: 10.1128/jvi.62.7.2329-2336.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Polo J. M., Davis N. L., Rice C. M., Huang H. V., Johnston R. E. Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro. J Virol. 1988 Jun;62(6):2124–2133. doi: 10.1128/jvi.62.6.2124-2133.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rice C. M., Levis R., Strauss J. H., Huang H. V. 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. J Virol. 1987 Dec;61(12):3809–3819. doi: 10.1128/jvi.61.12.3809-3819.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rice C. M., Strauss J. H. Association of sindbis virion glycoproteins and their precursors. J Mol Biol. 1982 Jan 15;154(2):325–348. doi: 10.1016/0022-2836(82)90067-5. [DOI] [PubMed] [Google Scholar]
  22. Rice C. M., Strauss J. H. Nucleotide sequence of the 26S mRNA of Sindbis virus and deduced sequence of the encoded virus structural proteins. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2062–2066. doi: 10.1073/pnas.78.4.2062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H. J., Johnson J. E., Kamer G., Luo M., Mosser A. G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
  24. Schmaljohn A. L., Kokubun K. M., Cole G. A. Protective monoclonal antibodies define maturational and pH-dependent antigenic changes in Sindbis virus E1 glycoprotein. Virology. 1983 Oct 15;130(1):144–154. doi: 10.1016/0042-6822(83)90124-1. [DOI] [PubMed] [Google Scholar]
  25. Sherman L. A., Griffin D. E. Pathogenesis of encephalitis induced in newborn mice by virulent and avirulent strains of Sindbis virus. J Virol. 1990 May;64(5):2041–2046. doi: 10.1128/jvi.64.5.2041-2046.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith A. L., Tignor G. H. Host cell receptors for two strains of Sindbis virus. Arch Virol. 1980;66(1):11–26. doi: 10.1007/BF01315041. [DOI] [PubMed] [Google Scholar]
  27. Stanley J., Cooper S. J., Griffin D. E. Alphavirus neurovirulence: monoclonal antibodies discriminating wild-type from neuroadapted Sindbis virus. J Virol. 1985 Oct;56(1):110–119. doi: 10.1128/jvi.56.1.110-119.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. TAYLOR R. M., HURLBUT H. S., WORK T. H., KINGSTON J. R., FROTHINGHAM T. E. Sindbis virus: a newly recognized arthropodtransmitted virus. Am J Trop Med Hyg. 1955 Sep;4(5):844–862. doi: 10.4269/ajtmh.1955.4.844. [DOI] [PubMed] [Google Scholar]

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