title: Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus.
abstract: Strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type II precursor glycans, and to restrict type II glycan binding in the bovine counterpart. Such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Liya
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Sasirekha
authors.initials: S
authors.lastname: Ramani
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Czako
authors.affiliation: Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.affiliation: Department of Biochemistry and the National Center for Functional Glycomics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and the National Center for Functional Glycomics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Smith
authors.affiliation: Department of Biochemistry and the National Center for Functional Glycomics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.|Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: B V
authors.initials: BV
authors.lastname: Venkataram Prasad
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism / Q000821:virology*; D005759:Gastroenteritis / Q000378:metabolism / Q000821:virology; D006801:Humans; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D016865:Reassortant Viruses / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D012401:Rotavirus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012400:Rotavirus Infections / Q000378:metabolism* / Q000662:veterinary* / Q000821:virology; D013045:Species Specificity; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011134:Polysaccharides; D011991:Receptors, Virus; D017361:Viral Nonstructural Proteins