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Related Experiment Videos

Differences in virion stability among Sindbis virus pathogenesis mutants.

S Gidwitz1, J M Polo, N L Davis

  • 1Department of Microbiology, North Carolina State University, Raleigh 27695-7615.

Virus Research
|May 1, 1988
PubMed
Summary

Closely related Sindbis virus strains show differences in virulence due to structural variations. An arginine substitution in the E2 glycoprotein reduces virion stability and mouse virulence, but instability alone doesn't cause reduced virulence.

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Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Sindbis virus (Sindbis virus) strains exhibit varying virulence in neonatal mice.
  • Understanding the structural basis of Sindbis virus virulence is crucial for disease control.

Purpose of the Study:

  • To investigate the structural differences between Sindbis virus strains with differing virulence.
  • To identify the molecular determinants responsible for Sindbis virus attenuation in neonatal mice.

Main Methods:

  • Sensitivity assays for heat, dithiothreitol (DTT), phenylglyoxal, and low pH.
  • Biochemical analysis including virion density and glycoprotein labeling ([14C]iodoacetamide).
  • Nucleotide sequence comparison and recombinant Sindbis virus clone analysis.

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Main Results:

  • Attenuated Sindbis virus mutants (SB-RL, SB-FP) showed increased sensitivity to heat and DTT compared to virulent strains (SB).
  • A specific amino acid substitution (arginine for serine at E2 position 114) in attenuated strains correlated with reduced virion stability and virulence.
  • Virion instability alone did not fully explain the reduced virulence in vivo, as shown by a virulent revertant retaining the E2 mutation.

Conclusions:

  • The E2 glycoprotein substitution (Arg114) is a key determinant of Sindbis virus attenuation in neonatal mice.
  • Reduced virion stability is linked to this E2 mutation but is not the sole factor driving reduced virulence.
  • Further research is needed to elucidate the complete mechanisms of Sindbis virus virulence and attenuation.