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

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms9346· OSTI ID:1256040
 [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

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02- 05CH11231
OSTI ID:
1256040
Journal Information:
Nature Communications, Vol. 6; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 45 works
Citation information provided by
Web of Science

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Cited By (14)

Human Milk Oligosaccharides as Promising Antivirals journal March 2018
“Stuck on sugars – how carbohydrates regulate cell adhesion, recognition, and signaling” journal July 2019
Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus journal October 2019
Histo-blood group antigens as receptors for rotavirus, new understanding on rotavirus epidemiology and vaccine strategy: Rotavirus host receptor and vaccine strategy journal January 2017
Glycan recognition in globally dominant human rotaviruses journal July 2018
Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection journal November 2018
P[8] and P[4] Rotavirus Infection Associated with Secretor Phenotypes Among Children in South China journal October 2016
Glycan Specificity of P[19] Rotavirus and Comparison with Those of Related P Genotypes journal August 2016
Generation of Infectious Recombinant Human Rotaviruses from Just 11 Cloned cDNAs Encoding the Rotavirus Genome journal February 2019
Structural basis of glycan specificity of P[19] VP8*: Implications for rotavirus zoonosis and evolution journal November 2017
Unraveling the role of the secretor antigen in human rotavirus attachment to histo-blood group antigens journal June 2019
Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins journal December 2019
Diversity in Rotavirus–Host Glycan Interactions: A “Sweet” Spectrum journal May 2016
Development and evaluation of two subunit vaccine candidates containing antigens of hepatitis E virus, rotavirus, and astrovirus journal May 2016

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