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Journal of Virology, December 2002, p. 12992-13000, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12992-13000.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Oligosaccharides as Receptors for JC Virus

Laboratory of Molecular and Cellular Pathology, School of Medicine, Hokkaido University, CREST, JST, Sapporo 060-8638,¹ Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan,² Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912³

Received 7 June 2002/ Accepted 11 September 2002

JC virus (JCV) belongs to the polyomavirus family of double-stranded DNA viruses and in humans causes a demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy. Its hemagglutination activity and entry into host cells have been reported to depend on an N-linked glycoprotein containing sialic acid. In order to identify the receptors of JCV, we generated virus-like particles (VLP) consisting of major viral capsid protein VP1. We then developed an indirect VLP overlay assay to detect VLP binding to glycoproteins and a panel of glycolipids. We found that VLP bound to sialoglycoproteins, including 1-acid glycoprotein, fetuin, and transferrin receptor, and that this binding depended on 2-3-linked sialic acids and N-linked sugar chains. Neoglycoproteins were synthesized by using ovalbumin and conjugation with oligosaccharides containing the terminal 2-3- or 2-6-linked sialic acid or the branched 2-6-linked sialic acid. We show that the neoglycoprotein containing the terminal 2-6-linked sialic acid had the highest affinity for VLP, inhibited the hemagglutination activity of VLP and JCV, and inhibited the attachment of VLP to cells. We also demonstrate that VLP bound to specific glycolipids, such as lactosylceramide, and gangliosides, including GM3, GD2, GD3, GD1b, GT1b, and GQ1b, and that VLP bound weakly to GD1a but did not bind to GM1a, GM2, or galactocerebroside. Furthermore, the neoglycoprotein containing the terminal 2-6-linked sialic acid and the ganglioside GT1b inhibited JCV infection in the susceptible cell line IMR-32. These results suggest that the oligosaccharides of glycoproteins and glycolipids work as JCV receptors and may be feasible as anti-JCV agents.

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