Histo-blood group antigens, specifically type A antigen, play an important role in rotavirus infection, evolution, and potential cross-species transmission.
The distal portion of rotavirus (RV) VP4 spike protein (VP8*) is implicated in binding to cellular receptors, thereby facilitating viral attachment and entry. While VP8* of some animal RVs engage sialic acid, human RVs often attach to and enter cells in a sialic acid-independent manner. A recent study demonstrated that the major human RVs (P4, P6, and P8) recognize human histo-blood group antigens (HBGAs). In this study, we performed a phylogenetic analysis of RVs and showed further variations of RV interaction with HBGAs. On the basis of the VP8* sequences, RVs are grouped into five P genogroups (PI to PV), of which PI, PIV, and PV mainly infect animals, PII infects humans, and PIII infects both animals and humans. The sialic acid-dependent RVs (P1, P2, P3, and P7) form a subcluster within PI, while all three major P genotypes of human RVs (P4, P6, and P8) are clustered in PII. We then characterized three human RVs (P9, P14, and P25) in PIII and observed a new pattern of binding to the type A antigen which is distinct from that of the PII RVs. The binding was demonstrated by hemagglutination and saliva binding assay using recombinant VP8* and native RVs. Homology modeling and mutagenesis study showed that the locations of the carbohydrate binding interfaces are shared with the sialic acid-dependent RVs, although different amino acids are involved. The PIII VP8* proteins also bind the A antigens of the porcine and bovine mucins, suggesting the A antigen as a possible factor for cross-species transmission of RVs. Our study suggests that HBGAs play an important role in RV infection and evolution.
Liu et al. (Wed,) studied this question.