Rotaviruses preferentially bind O-linked sialylglycoconjugates and sialomucins

Abstract

Rotaviruses are the most common cause of severe gastroenteritis in infants and children worldwide. Early events of virus binding and entry are the critical determinants of cellular permissiveness to rotavirus replication. The only known ligands for rotaviruses are sialic acids. We now report that simian rotaviruses bind preferentially to a subset of sialylated glycoconjugates, i.e. glycoproteins containing O-linked sialic acid moieties. Rotaviruses are able to distinguish between sialylated trisaccharide ligands presented as neoglycolipids. Higher avidity binding by rotaviruses is explained by multivalent binding to clustered sialic acid moieties. Our in vitro data are extended to explain the protective effect of mucins in the murine model of rotavirus disease and the specific binding by rotavirus to a high molecular weight sialomucin in the infant mouse intestine. Rotavirus binding to a sialomucin may be analogous to selectin-mediated mechanisms of cellular adhesion, and may be advantageous to the virus in the dynamic environment of the intestine.