
AbstractRotaviruses (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.
Models, Molecular, Rotavirus, 570, 1.1 Normal biological development and functioning, Science, Amino Acid Motifs, Viral Nonstructural Proteins, Low Birth Weight and Health of the Newborn, Crystallography, X-Ray, Article, Rotavirus Infections, Cell Line, Preterm, Models, Polysaccharides, Animals, Humans, Amino Acid Sequence, Conserved Sequence, Fucose, Pediatric, Crystallography, Binding Sites, Biomedical and Clinical Sciences, Q, Infant, Newborn, Infant, Molecular, RNA-Binding Proteins, Biological Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Foodborne Illness, Newborn, Mutation, X-Ray, Blood Group Antigens, Biochemistry and Cell Biology, Digestive Diseases
Models, Molecular, Rotavirus, 570, 1.1 Normal biological development and functioning, Science, Amino Acid Motifs, Viral Nonstructural Proteins, Low Birth Weight and Health of the Newborn, Crystallography, X-Ray, Article, Rotavirus Infections, Cell Line, Preterm, Models, Polysaccharides, Animals, Humans, Amino Acid Sequence, Conserved Sequence, Fucose, Pediatric, Crystallography, Binding Sites, Biomedical and Clinical Sciences, Q, Infant, Newborn, Infant, Molecular, RNA-Binding Proteins, Biological Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Foodborne Illness, Newborn, Mutation, X-Ray, Blood Group Antigens, Biochemistry and Cell Biology, Digestive Diseases
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