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J Virol, June 1998, p. 4643-4649, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Infection of Glial Cells by the Human Polyomavirus JC Is Mediated by an N-Linked Glycoprotein Containing Terminal alpha (2-6)-Linked Sialic Acids

Christine K. Liu, Grant Wei, and Walter J. Atwood*

Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912

Received 9 December 1997/Accepted 19 February 1998

The human JC polyomavirus (JCV) is the etiologic agent of the fatal central nervous system (CNS) demyelinating disease progressive multifocal leukoencephalopathy (PML). PML typically occurs in immunosuppressed patients and is the direct result of JCV infection of oligodendrocytes. The initial event in infection of cells by JCV is attachment of the virus to receptors present on the surface of a susceptible cell. Our laboratory has been studying this critical event in the life cycle of JCV, and we have found that JCV binds to a limited number of cell surface receptors on human glial cells that are not shared by the related polyomavirus simian virus 40 (C. K. Liu, A. P. Hope, and W. J. Atwood, J. Neurovirol. 4:49-58, 1998). To further characterize specific JCV receptors on human glial cells, we tested specific neuraminidases, proteases, and phospholipases for the ability to inhibit JCV binding to and infection of glial cells. Several of the enzymes tested were capable of inhibiting virus binding to cells, but only neuraminidase was capable of inhibiting infection. The ability of neuraminidase to inhibit infection correlated with its ability to remove both alpha (2-3)- and alpha (2-6)-linked sialic acids from glial cells. A recombinant neuraminidase that specifically removes the alpha (2-3) linkage of sialic acid had no effect on virus binding or infection. A competition assay between virus and sialic acid-specific lectins that recognize either the alpha (2-3) or the alpha (2-6) linkage revealed that JCV preferentially interacts with alpha (2-6)-linked sialic acids on glial cells. Treatment of glial cells with tunicamycin, but not with benzyl N-acetyl-alpha -D-galactosaminide, inhibited infection by JCV, indicating that the sialylated JCV receptor is an N-linked glycoprotein. As sialic acid containing glycoproteins play a fundamental role in mediating many virus-cell and cell-cell recognition processes, it will be of interest to determine what role these receptors play in the pathogenesis of PML.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Brown University, Box G-B616, 117 Meeting St., Providence, RI 02912. Phone: (401) 863-3116. Fax: (401) 863-1971. E-mail: Walter_Atwood{at}Brown.edu.

J Virol, June 1998, p. 4643-4649, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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