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Title: Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

We report that 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. In conclusion, 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:
 [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [4] ;  [4] ;  [2] ;  [5]
  1. Baylor College of Medicine, Houston, TX (United States). Verna and Marrs McLean Department of Biochemistry and Molecular Biology
  2. Baylor College of Medicine, Houston, TX (United States). Department of Molecular Virology and Microbiology
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Emory Univ.School of Medicine, Atlanta, GA (United States)
  5. Baylor College of Medicine, Houston, TX (United States). Verna and Marrs McLean Department of Biochemistry and Molecular Biology; Baylor College of Medicine, Houston, TX (United States). Department of Molecular Virology and Microbiology
Publication Date:
OSTI Identifier:
1256040
Grant/Contract Number:
AC02- 05CH11231
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES