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Journal of Virology, November 2002, p. 11265-11272, Vol. 76, No. 22
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.22.11265-11272.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Sialic Acid Functions in Enterovirus 70 Binding and Infection
David A. Alexander and Kenneth Dimock*
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
Received 15 April 2002/
Accepted 13 August 2002
The interaction of viruses with host cell receptors is the initial step in viral infection and is an important determinant of virus host range, tissue tropism, and pathogenesis. The complement regulatory protein decay-accelerating factor (DAF/CD55) is an attachment receptor for enterovirus 70 (EV70), a member of the Picornaviridae, commonly associated with an eye infection in humans known as acute hemorrhagic conjunctivitis. In early work, the EV70 receptor on erythrocytes, responsible for its hemagglutinating activity, was shown to be sensitive to neuraminidase, implying an essential role for sialic acid in virus attachment. Here, we extend these results to show that cell surface sialic acid is required for EV70 binding to nucleated cells susceptible to virus infection and that sialic acid binding is important in productive infection. Through the use of site-directed mutagenesis to eliminate the single N-linked glycosylation site of DAF and of a chimeric receptor protein in which the O-glycosylated domain of DAF was replaced by a region of the HLA-B44 molecule, a role in EV70 binding for the sialic acid residues of DAF was excluded, suggesting the existence of at least one additional, sialylated EV70-binding factor at the cell surface. Treatment of cells with metabolic inhibitors of glycosylation excluded a role for the N-linked oligosaccharides of glycoproteins but suggested that O-linked glycosylation is important for EV70 binding.
* Corresponding author. Mailing address: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Rd., Ottawa, Ontario K1H 8M5, Canada. Phone: (613) 562-5800, ext. 8311. Fax: (613) 562-5800. E-mail:
kdimock{at}uottawa.ca.
Journal of Virology, November 2002, p. 11265-11272, Vol. 76, No. 22
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.22.11265-11272.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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