Oligosaccharides as receptors for JC virus

被引:85
作者
Komagome, R
Sawa, H
Suzuki, T
Suzuki, Y
Tanaka, S
Atwood, WJ
Nagashima, K
机构
[1] Hokkaido Univ, Sch Med, Lab Mol & Cellular Pathol,JST,CREST, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[2] Univ Shizuoka, Sch Pharmaceut Sci, Dept Biochem, Shizuoka 4228526, Japan
[3] Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA
关键词
D O I
10.1128/JVI.76.24.12992-13000.2002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 alpha1-acid glycoprotein, fetuin, and transferrin receptor, and that this binding depended on alpha2-3-linked sialic acids and N-linked sugar chains. Neoglycoproteins were synthesized by using ovalbumin and conjugation with oligosaccharides containing the terminal alpha2-3- or alpha2-6-linked sialic acid or the branched alpha2-6-linked sialic acid. We show that the neoglycoprotein containing the terminal alpha2-6-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 alpha2-6-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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页码:12992 / 13000
页数:9
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