Glycan recognition in globally dominant human rotaviruses

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Rotaviruses (RVs) are a major cause of severe diarrhea in children globally.
• Histo-blood group antigens (HBGA) are crucial for RV attachment and infection.
• The interaction mechanisms between dominant RV genotypes (P[4], P[6], P[8]) and HBGA remain unclear.

Purpose of the Study:

• To elucidate the structural basis of HBGA binding by globally dominant human rotavirus genotypes.
• To investigate the structural determinants of age-restricted tropism observed in neonatal rotavirus P[6] strains.

Main Methods:

• X-ray crystallography was used to determine the structures of P[4] and P[6] VP8* proteins.
• Structures were solved for VP8* proteins alone and in complex with H-type I HBGA.
• Structural comparisons were made between neonatal P[6] VP8* and other dominant RV genotypes.

Main Results:

• A conserved glycan binding site in VP8* was identified across globally dominant RV genotypes, enabling ABH HBGA binding.
• Neonatal P[6] VP8* exhibited subtle structural alterations in the glycan binding site.
• These alterations may limit the binding of branched glycans by neonatal P[6] RVs.

Conclusions:

• The findings provide a structural explanation for the prevalence of specific HBGA-binding RV genotypes.
• Structural changes in neonatal P[6] VP8* correlate with age-restricted tropism.
• Developmentally regulated glycan availability in the neonatal gut likely influences P[6] RV tropism.