Glycan recognition in globally dominant human rotaviruses

Liya Hu, Banumathi Sankaran, Daniel R. Laucirica, Ketki Patil, Wilhelm Salmen, Allan Chris M Ferreon, Phoebe S. Tsoi, Yi Lasanajak, David F. Smith, Sasirekha Ramani, Robert L. Atmar, Mary K. Estes, Josephine C. Ferreon and B. V. Venkataram Prasad ()
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Liya Hu: Baylor College of Medicine
Banumathi Sankaran: Lawrence Berkeley National Laboratory
Daniel R. Laucirica: Baylor College of Medicine
Ketki Patil: Baylor College of Medicine
Wilhelm Salmen: Baylor College of Medicine
Allan Chris M Ferreon: Baylor College of Medicine
Phoebe S. Tsoi: Baylor College of Medicine
Yi Lasanajak: Emory University School of Medicine
David F. Smith: Emory University School of Medicine
Sasirekha Ramani: Baylor College of Medicine
Robert L. Atmar: Baylor College of Medicine
Mary K. Estes: Baylor College of Medicine
Josephine C. Ferreon: Baylor College of Medicine
B. V. Venkataram Prasad: Baylor College of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05098-4

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