alpha 2-3- and alpha 2-6- N-linked sialic acids allow efficient interaction of Newcastle Disease Virus with target cells

Receptor recognition and binding is the first step in the viral cycle. It has been established that Newcastle Disease Virus (NDV) interacts with sialylated molecules such as gangliosides and glycoproteins at the cell surface. Nevertheless, the specific receptor(s) that mediate virus entry are not well known. We have analysed the role of the sialic acid linkage in the early steps of the viral infection cycle. Pretreatment of ELL-0 cells with both alpha 2,3 and alpha 2,6 specific sialidases led to the inhibition of NDV binding, fusion and infectivity, which were restored after alpha 2,3(N)- and alpha 2,6(N)-sialyltransferase incubation. Moreover, alpha 2,6(N)-sialyltransferases also restored NDV activities in alpha 2-6-linked sialic acid deficient cells. Competition with alpha 2-6 sialic acid-binding lectins led to a reduction in the three NDV activities (binding, fusion and infectivity) suggesting a role for alpha 2-6- linked sialic acid in NDV entry. We conclude that both alpha 2-3- and alpha 2-6- linked sialic acid containing glycoconjugates may be used for NDV infection. NDV was able to efficiently bind, fuse and infect the ganglioside-deficient cell line GM95 to a similar extent to that of its parental MEB4, suggesting that gangliosides are not essential for NDV binding, fusion and infectivity. Nevertheless, the fact that the interaction of NDV with cells deficient in N-glycoprotein expression such as Lec1 was less efficient prompted us to conclude that NDV requires N-linked glycoproteins for efficient attachment and entry into the host cell.