Structural plasticity of the Semliki Forest virus glycome upon interspecies transmission

J Proteome Res. 2014 Mar 7;13(3):1702-12. doi: 10.1021/pr401162k. Epub 2014 Feb 10.

Abstract

Cross-species viral transmission subjects parent and progeny alphaviruses to differential post-translational processing of viral envelope glycoproteins. Alphavirus biogenesis has been extensively studied, and the Semliki Forest virus E1 and E2 glycoproteins have been shown to exhibit differing degrees of processing of N-linked glycans. However the composition of these glycans, including that arising from different host cells, has not been determined. Here we determined the chemical composition of the glycans from the prototypic alphavirus, Semliki Forest virus, propagated in both arthropod and rodent cell lines, by using ion-mobility mass spectrometry and collision-induced dissociation analysis. We observe that both the membrane-proximal E1 fusion glycoprotein and the protruding E2 attachment glycoprotein display heterogeneous glycosylation that contains N-linked glycans exhibiting both limited and extensive processing. However, E1 contained predominantly highly processed glycans dependent on the host cell, with rodent and mosquito-derived E1 exhibiting complex-type and paucimannose-type glycosylation, respectively. In contrast, the protruding E2 attachment glycoprotein primarily contained conserved under-processed oligomannose-type structures when produced in both rodent and mosquito cell lines. It is likely that glycan processing of E2 is structurally restricted by steric-hindrance imposed by local viral protein structure. This contrasts E1, which presents glycans characteristic of the host cell and is accessible to enzymes. We integrated our findings with previous cryo-electron microscopy and crystallographic analyses to produce a detailed model of the glycosylated mature virion surface. Taken together, these data reveal the degree to which virally encoded protein structure and cellular processing enzymes shape the virion glycome during interspecies transmission of Semliki Forest virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes
  • Animals
  • Carbohydrate Sequence
  • Cell Line
  • Cricetinae
  • Glycomics
  • Glycosylation
  • Host Specificity
  • Mass Spectrometry / methods
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Polysaccharides / analysis*
  • Polysaccharides / chemistry
  • Protein Processing, Post-Translational*
  • Semliki forest virus / chemistry*
  • Semliki forest virus / metabolism
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / metabolism
  • Virion / chemistry*
  • Virion / metabolism

Substances

  • E1 glycoprotein, Semliki forest virus
  • Membrane Glycoproteins
  • Polysaccharides
  • Viral Envelope Proteins