by
Liya Hu;
Banumathi Sankaran;
Daniel R. Laucirica;
Ketki Patil;
Wilhelm Salmen;
Allan Chris M Ferreon;
Phoebe S. Tsoi;
Yi Lasanajak;
David Smith;
Sasirekha Ramani;
Robert L. Atmar;
Mary K. Estes;
Josephine C. Ferreon;
B.V. Venkataram Prasad
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.