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Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages
Department of Microbiology and Infectious Diseases, Flinders University, Flinders Medical Centre, Bedford Park, SA 5042, Australia
Department of Microbiology and Infectious Diseases, SA Pathology, Flinders Medical Centre, Bedford Park, SA 5042, Australia
* Author to whom correspondence should be addressed.
Received: 31 October 2012; in revised form: 10 December 2012 / Accepted: 10 December 2012 / Published: 14 December 2012
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.
Keywords: human metapneumovirus (hMPV); Glycosaminoglycan (GAG); G protein; F protein; infectivity
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Adamson, P.; Thammawat, S.; Muchondo, G.; Sadlon, T.; Gordon, D. Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages. Viruses 2012, 4, 3785-3803.
Adamson P, Thammawat S, Muchondo G, Sadlon T, Gordon D. Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages. Viruses. 2012; 4(12):3785-3803.
Adamson, Penelope; Thammawat, Sutthiwan; Muchondo, Gamaliel; Sadlon, Tania; Gordon, David. 2012. "Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages." Viruses 4, no. 12: 3785-3803.