Revisiting the role of histo-blood group antigens in rotavirus host-cell invasion

Histo-blood group antigens (HBGAs) have been proposed as rotavirus receptors. H type-1 and Lewisb antigens have been reported to bind VP8* from major human rotavirus genotypes P[4], P[6] and P[8], while VP8* from a rarer P[14] rotavirus recognizes A-type HBGAs. However, the role and significance of HBGA receptors in rotavirus pathogenesis remains uncertain. Here we report that P[14] rotavirus HAL1166 and the related P[9] human rotavirus K8 bind to A-type HBGAs, although neither virus engages the HBGA-specific α1,2-linked fucose moiety. Notably, human rotaviruses DS-1 (P[4]) and RV-3 (P[6]) also use A-type HBGAs for infection, with fucose involvement. However, human P[8] rotavirus Wa does not recognize A-type HBGAs. Furthermore, the common human rotaviruses that we have investigated do not use Lewisb and H type-1 antigens. Our results indicate that A-type HBGAs are receptors for human rotaviruses, although rotavirus strains vary in their ability to recognize these antigens. Histo-blood group antigens (HBGAs) have been proposed as essential cellular receptors for rotaviruses, which can cause severe diarrhoea in children. Here, the authors show that rotavirus strains display important variations in their ability to recognize different HBGAs.