Sialic acid is a cellular receptor for coxsackievirus A24 variant, an emerging virus with pandemic potential

Department of Clinical Microbiology, Division of Virology, Umeå University, Umeå, SE-901 85, Sweden; Department of Chemistry, Umeå University, Umeå, SE-901 87, Sweden; Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA

^* To whom correspondence should be addressed. Email: niklas.arnberg{at}climi.umu.se.

	Abstract

Binding to target cell receptors is a critical step in the virus life cycle. Coxsackievirus A24 variant (CVA24v) has pandemic potential and is a major cause of acute hemorrhagic conjunctivitis, but its cellular receptor has hitherto been unknown. Here we show that CVA24v fails to bind to and infect CHO cells defective in sialic acid expression. Binding of CVA24v to and infection of corneal epithelial cells is efficiently inhibited by treating cells with a sialic acid-cleaving enzyme or sialic acid-binding lectins, and by treatment of the virus with soluble, multivalent sialic acid. Protease treatment of cells efficiently inhibited virus binding, suggesting that the receptor is a sialylated glycoprotein. Besides enterovirus type 70 and influenza A virus, CVA24v also causes pandemics. Remarkably, all three viruses use the same receptor. Since several unrelated viruses with tropism for the eye use this receptor, sialic acid-based antiviral drugs that prevent virus entry may be useful for topical treatment of such infections.