Histo-blood group antigens as divergent factors of groups A and C rotaviruses circulating in humans and different animal species.

Histo-blood group antigens (HBGAs) have been found to be important host susceptibility factors or receptors for human rotavirus (RVs) with genotype-specific host ranges, impacting the disease patterns, epidemiology, and strategy development against RV diseases in humans. However, how the glycan factors contribute to RV diversity and host ranges to different animal species remains unclear. In this study using recombinant VP8* proteins as probes to perform glycan array analyses of RVs, we observed a wide range of glycan-binding profiles, including those binding to sialic acid-containing glycans, among group A (RVA) and group C (RVC) RVs that mainly infect different animal species. A tri-saccharide glycan Galα1-3Galβ1-4Glc containing a terminal α-Gal was recognised by multiple RVA/RVC genotypes, providing valuable information on RV evolution under selection of the step-wisely synthesised HBGAs in many animals before they were introduced to humans to be human pathogens. Saliva binding studies of VP8* also revealed strain-specific host ranges or species barriers between humans and these animal RV genotypes, further improved our understanding on RV host ranges, disease burdens, epidemiology, and vaccine strategy against RVs.