# Specific binding of human P[28] rotavirus VP8* protein to blood group ABH antigens on type 1 chains

## TL;DR

The study reveals that the P[28] rotavirus can bind to human blood group antigens, suggesting a potential for future epidemics and the need for surveillance.

## Contribution

The study identifies the specific binding of P[28] rotavirus VP8* to blood group antigens on type 1 chains, a novel finding for this genogroup.

## Key findings

- P[28]-VP8* binds to blood group A, B, and H(O) antigens on type 1 chains.
- P[28]-VP8* does not bind to Lewis epitopes or mucin O-glycan cores.
- The broad HBGA binding of P[28]-VP8* raises concerns about potential future epidemics.

## Abstract

Group A rotavirus (RV) has been the major cause of acute gastroenteritis in infants and young children. Among the five P genogroups almost all P genotype RVs in P[II], P[III] and P[IV] genogroups that infect humans can bind glycan histo-blood group antigens (HBGAs) as the receptors on the host cell surface to infect host through the viral spike protein VP8*. Although P[I] is the largest genogroup, P[28] and P[10] are the only two genotype RVs infecting humans in the group. It has recently been found that a P[28] strain is related to bat RV and considered a possible product of reassortment between bat and human RVs. Bats are increasingly being recognized as an important reservoir for viruses crossing species barriers to infect humans. Unrevealing the interactions between RVs and host receptors is important for understanding RV evolution, infection, and epidemic. In the present study, using a multiphasic approach, including X-ray crystallography, glycan microarray with a dedicated probe library, bio-layer interferometry, site-specific mutagenesis, and molecular docking and dynamics simulations, we found that P[28]-VP8* can bind to all blood group A, B and H(O) antigens but on type 1 chain only, without the capability to bind to any Lewis epitopes or mucin O-glycan cores. Different from most of the prevalent human RVs, such as P[8], P[4] and P[6], the broad HBGA binding specificity of P[28]-VP8* and the fact of the recently identified a possible reassortment P[28] strain of bat and human RVs have raised the concern of a future possibility of P[I] genogroup RV epidemic. RV surveillance may also need to take the P[I] genogroup RVs into account in the future.

Rotaviruses (RVs) are the main cause of severe diarrhea in young children. Glycans have been documented as the major receptors for many RVs of the P[II], P[III] and P[IV] genogroups, but we know very little about the glycan receptors of P[I] genogroup RVs. In this study, we used glycan microarray, bio-layer interferometry and X-ray crystallography to investigate the structure details responsible for the interactions of the VP8* spike protein of P[28] RV with type 1 blood group ABH(O) antigens. P[28] has been reported as one of the two genotype viruses in the P[I] group to infect humans. The broad histo-blood group antigens binding specificity and the recently found a possible P[28] reassortment strain of bat and human RVs may indicate a possibility of P[I] group RV epidemic and necessity of future RV surveillance.