Glycan recognition in globally dominant human rotaviruses

• Published in: Nature communications Vol. 9; no. 1; pp. 2631 - 12
• Main Authors: Hu, Liya, Sankaran, Banumathi, Laucirica, Daniel R., Patil, Ketki, Salmen, Wilhelm, Ferreon, Allan Chris M, Tsoi, Phoebe S., Lasanajak, Yi, Smith, David F., Ramani, Sasirekha, Atmar, Robert L., Estes, Mary K., Ferreon, Josephine C., Prasad, B. V. Venkataram
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.07.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 631/326/596/1794; 631/326/596/2557; 631/45/72; 631/535/1266; Age; Antigens; BASIC BIOLOGICAL SCIENCES; Binding sites; Blood groups; Cell adhesion; Children; Crystal structure; Diarrhea; Epidemiology; Genotypes; Glycan; Humanities and Social Sciences; Infants; multidisciplinary; Neonates; Polysaccharides; Rotavirus; Science; Science (multidisciplinary); Tropism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05098-4

Rotaviruses (RVs) cause life-threatening diarrhea in infants and children worldwide. Recent biochemical and epidemiological studies underscore the importance of histo-blood group antigens (HBGA) as both cell attachment and susceptibility factors for the globally dominant P[4], P[6], and P[8] genotypes of human RVs. How these genotypes interact with HBGA is not known. Here, our crystal structures of P[4] and a neonate-specific P[6] VP8*s alone and in complex with H-type I HBGA reveal a unique glycan binding site that is conserved in the globally dominant genotypes and allows for the binding of ABH HBGAs, consistent with their prevalence. Remarkably, the VP8* of P[6] RVs isolated from neonates displays subtle structural changes in this binding site that may restrict its ability to bind branched glycans. This provides a structural basis for the age-restricted tropism of some P[6] RVs as developmentally regulated unbranched glycans are more abundant in the neonatal gut. Human rotaviruses (RV) bind to histo-blood group antigens (HBGA) for attachment, but how different viral genotypes interact with HBGA isn’t known. Here, Hu et al . report crystal structures of a prevalent and a neonate-specific RV in complex with HBGA and provide insights into glycan recognition and age-restricted tropism of RVs.