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.