Novel structural insights into rotavirus recognition of ganglioside glycan receptors

Abstract

Rotaviruses ubiquitously infect children under the age of 5, being responsible for more than half a million diarrhoeal deaths each year worldwide. Host cell oligosaccharides containing sialic acid(s) are critical for attachment by rotaviruses. However to date no detailed three-dimensional atomic model showing the exact rotavirus interactions with these glycoconjugate receptors has been reported. Here we present the first crystallographic structures of the rotavirus carbohydrate-recognizing protein VP8* in complex with ganglioside GM3 glycans. In combination with assessment of the inhibition of rotavirus infectivity by N-acetyl- and N-glycolyl- forms of this ganglioside, our results reveal key details of rotavirus-ganglioside GM3 glycan recognition. In addition, they show a direct correlation between the carbohydrate specificities exhibited by VP8* from porcine and by monkey rotaviruses and the respective infectious virus particles. These novel results also indicate the potential binding interactions of rotavirus VP8* with other sialic acid-containing gangliosides.