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Oligosaccharides as receptors for JC virus
Rika Komagome1, Hirofumi Sawa, Takashi Suzuki
1Laboratory of Molecular and Cellular Pathology, School of Medicine, Hokkaido University, CREST, JST, N15 W7, Kita-ku, Sapporo 060-8638, Japan.
Journal of Virology
|November 20, 2002
Summary
JC virus (JCV) uses specific sugar structures on glycoproteins and glycolipids as receptors for cell entry. These identified JCV receptors, particularly those with alpha2-6-linked sialic acid, show potential as therapeutic agents against JCV infection.
Area of Science:
- Virology
- Glycobiology
- Neuroscience
Background:
- JC virus (JCV) is a human polyomavirus causing progressive multifocal leukoencephalopathy (PML), a CNS demyelinating disease.
- JCV hemagglutination and cell entry are known to involve N-linked glycoproteins with sialic acid.
Purpose of the Study:
- To identify the specific receptors for JC virus (JCV) on host cells.
- To investigate the role of glycoproteins and glycolipids in JCV attachment and infection.
Main Methods:
- Generation of virus-like particles (VLPs) from the major viral capsid protein VP1.
- Development of an indirect VLP overlay assay to detect binding to various glycoproteins and glycolipids.
- Synthesis of neoglycoproteins with defined sialic acid linkages for binding and inhibition assays.
Main Results:
- VLPs bound to sialoglycoproteins (e.g., fetuin) and specific glycolipids (e.g., gangliosides GT1b, GM3).
- Binding was dependent on alpha2-3-linked sialic acids and N-linked sugar chains, with highest affinity for terminal alpha2-6-linked sialic acid.
- Neoglycoproteins with terminal alpha2-6-linked sialic acid and ganglioside GT1b inhibited JCV hemagglutination, VLP cell attachment, and JCV infection in IMR-32 cells.
Conclusions:
- Oligosaccharides on glycoproteins and glycolipids function as JC virus receptors.
- Specific structures, like terminal alpha2-6-linked sialic acid and GT1b, are key for JCV binding and infection.
- These identified receptors represent potential targets for novel anti-JCV therapeutic agents.