title: N-glycolyl GM1 ganglioside as a receptor for simian virus 40.
abstract: Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus.
authors.affiliation: Glycosciences Laboratory, Faculty of Medicine, Imperial College London, Northwick Park and St. Mark's Campus, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Campanero-Rhodes
authors.forename: Alicia
authors.initials: A
authors.lastname: Smith
authors.forename: Wengang
authors.initials: W
authors.lastname: Chai
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
authors.forename: Robert A
authors.initials: RA
authors.lastname: Childs
authors.forename: Yibing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Helge
authors.initials: H
authors.lastname: Ewers
authors.forename: Ari
authors.initials: A
authors.lastname: Helenius
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Ten
authors.initials: T
authors.lastname: Feizi
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry; D002460:Cell Line; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry* / Q000502:physiology*; D013539:Simian virus 40 / Q000502:physiology*; D053585:Virus Attachment
chemical_list: D036022:Capsid Proteins; D011991:Receptors, Virus; C062481:VP1 protein, polyomavirus; D005677:G(M1) Ganglioside