Diversity in glycosaminoglycan binding amongst hMPV G protein lineages

Viruses. 2012 Dec 14;4(12):3785-803. doi: 10.3390/v4123785.

Abstract

We have previously shown that hMPV G protein (B2 lineage) interacts with cellular glycosaminoglycans (GAGs). In this study we examined subtypes A1, A2 and B1 for this interaction. GAG-dependent infectivity of available hMPV strains was demonstrated using GAG-deficient cells and heparin competition. We expressed the G protein ectodomains from all strains and analysed these by heparin affinity chromatography. In contrast to the B2 lineage, neither the A2 or B1 G proteins bound to heparin. Sequence analysis of these strains indicated that although there was some homology with the B2 heparin-binding domains, there were less positively charged residues, providing a likely explanation for the lack of binding. Although sequence analysis did not demonstrate well defined positively charged domains in G protein of the A1 strain, this protein was able to bind heparin, albeit with a lower affinity than G protein of the B2 strain. These results indicate diversity in GAG interactions between G proteins of different lineages and suggest that the GAG-dependency of all strains may be mediated by interaction with an alternative surface protein, most probably the conserved fusion (F) protein. Analysis of both native and recombinant F protein confirmed that F protein binds heparin, supporting this conclusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chromatography
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Glycosaminoglycans / metabolism*
  • Heparin / metabolism
  • Humans
  • Metapneumovirus / genetics
  • Metapneumovirus / physiology*
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Viral Fusion Proteins / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Attachment

Substances

  • G glycoprotein, human metapneumovirus
  • Glycoproteins
  • Glycosaminoglycans
  • Viral Fusion Proteins
  • Viral Proteins
  • Heparin