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

Abstract

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:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1256040
Grant/Contract Number:  
AC02- 05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Hu, Liya, Ramani, Sasirekha, Czako, Rita, Sankaran, Banumathi, Yu, Ying, Smith, David F., Cummings, Richard D., Estes, Mary K., and Venkataram Prasad, B. V. Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus. United States: N. p., 2015. Web. doi:10.1038/ncomms9346.
Hu, Liya, Ramani, Sasirekha, Czako, Rita, Sankaran, Banumathi, Yu, Ying, Smith, David F., Cummings, Richard D., Estes, Mary K., & Venkataram Prasad, B. V. Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus. United States. doi:10.1038/ncomms9346.
Hu, Liya, Ramani, Sasirekha, Czako, Rita, Sankaran, Banumathi, Yu, Ying, Smith, David F., Cummings, Richard D., Estes, Mary K., and Venkataram Prasad, B. V. Wed . "Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus". United States. doi:10.1038/ncomms9346. https://www.osti.gov/servlets/purl/1256040.
@article{osti_1256040,
title = {Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus},
author = {Hu, Liya and Ramani, Sasirekha and Czako, Rita and Sankaran, Banumathi and Yu, Ying and Smith, David F. and Cummings, Richard D. and Estes, Mary K. and Venkataram Prasad, B. V.},
abstractNote = {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.},
doi = {10.1038/ncomms9346},
journal = {Nature Communications},
number = ,
volume = 6,
place = {United States},
year = {2015},
month = {9}
}

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Works referenced in this record:

The sweet spot: defining virus–sialic acid interactions
journal, September 2014

  • Stencel-Baerenwald, Jennifer E.; Reiss, Kerstin; Reiter, Dirk M.
  • Nature Reviews Microbiology, Vol. 12, Issue 11
  • DOI: 10.1038/nrmicro3346

Investigating virus–glycan interactions using glycan microarrays
journal, August 2014


Zoonotic aspects of rotaviruses
journal, January 2010


Rotavirus vaccines: recent developments and future considerations
journal, July 2007

  • Angel, Juana; Franco, Manuel A.; Greenberg, Harry B.
  • Nature Reviews Microbiology, Vol. 5, Issue 7
  • DOI: 10.1038/nrmicro1692

Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG)
journal, May 2011

  • Matthijnssens, Jelle; Ciarlet, Max; McDonald, Sarah M.
  • Archives of Virology, Vol. 156, Issue 8
  • DOI: 10.1007/s00705-011-1006-z

Identification of an avian group A rotavirus containing a novel VP4 gene with a close relationship to those of mammalian rotaviruses
journal, January 2013

  • Reetz, Jochen; Twardziok, Sven; Sachsenröder, Jana
  • Journal of General Virology, Vol. 94, Issue 1
  • DOI: 10.1099/vir.0.047381-0

Sialic acid dependence in rotavirus host cell invasion
journal, December 2008

  • Haselhorst, Thomas; Fleming, Fiona E.; Dyason, Jeffrey C.
  • Nature Chemical Biology, Vol. 5, Issue 2
  • DOI: 10.1038/nchembio.134

Revisiting the role of histo-blood group antigens in rotavirus host-cell invasion
journal, January 2015

  • Böhm, Raphael; Fleming, Fiona E.; Maggioni, Andrea
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms6907

Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen
journal, April 2012

  • Hu, Liya; Crawford, Sue E.; Czako, Rita
  • Nature, Vol. 485, Issue 7397
  • DOI: 10.1038/nature10996

Spike Protein VP8* of Human Rotavirus Recognizes Histo-Blood Group Antigens in a Type-Specific Manner
journal, February 2012


Both Lewis and Secretor Status Mediate Susceptibility to Rotavirus Infections in a Rotavirus Genotype–Dependent Manner
journal, August 2014

  • Nordgren, Johan; Sharma, Sumit; Bucardo, Filemon
  • Clinical Infectious Diseases, Vol. 59, Issue 11
  • DOI: 10.1093/cid/ciu633

A FUT2 Gene Common Polymorphism Determines Resistance to Rotavirus A of the P[8] Genotype
journal, November 2013

  • Imbert-Marcille, Berthe-Marie; Barbé, Laure; Dupé, Mathilde
  • The Journal of Infectious Diseases, Vol. 209, Issue 8
  • DOI: 10.1093/infdis/jit655

Rotavirus Infection in the Neonatal Nurseries of a Tertiary Care Hospital in India
journal, January 2008

  • Ramani, Sasirekha; Sowmyanarayanan, Thuppal V.; Gladstone, Beryl Primrose
  • The Pediatric Infectious Disease Journal, Vol. 27, Issue 8
  • DOI: 10.1097/INF.0b013e3181715170

Comparison of viral load and duration of virus shedding in symptomatic and asymptomatic neonatal rotavirus infections
journal, September 2010

  • Ramani, Sasirekha; Sankaran, Premi; Arumugam, Rajesh
  • Journal of Medical Virology, Vol. 82, Issue 10
  • DOI: 10.1002/jmv.21872

First rotavirus vaccine made in India is launched
journal, March 2015


The VP8* Domain of Neonatal Rotavirus Strain G10P[11] Binds to Type II Precursor Glycans
journal, April 2013

  • Ramani, S.; Cortes-Penfield, N. W.; Hu, L.
  • Journal of Virology, Vol. 87, Issue 13
  • DOI: 10.1128/JVI.03518-12

Poly-LacNAc as an Age-Specific Ligand for Rotavirus P[11] in Neonates and Infants
journal, November 2013


Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses
journal, July 2014

  • Yu, Ying; Lasanajak, Yi; Song, Xuezheng
  • Molecular & Cellular Proteomics, Vol. 13, Issue 11
  • DOI: 10.1074/mcp.M114.039875

Structural Characterization by Multistage Mass Spectrometry (MS n ) of Human Milk Glycans Recognized by Human Rotaviruses
journal, July 2014

  • Ashline, David J.; Yu, Ying; Lasanajak, Yi
  • Molecular & Cellular Proteomics, Vol. 13, Issue 11
  • DOI: 10.1074/mcp.M114.039925

Glycan-dependent viral infection in infants and the role of human milk oligosaccharides
journal, August 2014


High-Resolution Molecular and Antigen Structure of the VP8* Core of a Sialic Acid-Independent Human Rotavirus Strain
journal, January 2006


AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
journal, December 2009

  • Morris, Garrett M.; Huey, Ruth; Lindstrom, William
  • Journal of Computational Chemistry, Vol. 30, Issue 16
  • DOI: 10.1002/jcc.21256

Novel Structural Insights into Rotavirus Recognition of Ganglioside Glycan Receptors
journal, November 2011

  • Yu, Xing; Coulson, Barbara S.; Fleming, Fiona E.
  • Journal of Molecular Biology, Vol. 413, Issue 5
  • DOI: 10.1016/j.jmb.2011.09.005

Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate
journal, July 2014


The Predominance of Type I Oligosaccharides Is a Feature Specific to Human Breast Milk
journal, May 2012

  • Urashima, Tadasu; Asakuma, Sadaki; Leo, Fiame
  • Advances in Nutrition, Vol. 3, Issue 3
  • DOI: 10.3945/an.111.001412

Recent Advances in Studies on Milk Oligosaccharides of Cows and Other Domestic Farm Animals
journal, March 2013

  • Urashima, Tadasu; Taufik, Epi; Fukuda, Kenji
  • Bioscience, Biotechnology, and Biochemistry, Vol. 77, Issue 3
  • DOI: 10.1271/bbb.120810

The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine
journal, May 2011

  • Muglia, C.; Mercer, N.; Toscano, M. A.
  • Cell Death & Disease, Vol. 2, Issue 5
  • DOI: 10.1038/cddis.2011.44

Galectin-3 Interactions with Glycosphingolipids
journal, April 2014

  • Collins, Patrick M.; Bum-Erdene, Khuchtumur; Yu, Xing
  • Journal of Molecular Biology, Vol. 426, Issue 7
  • DOI: 10.1016/j.jmb.2013.12.004

Microbe–Host Interactions are Positively and Negatively Regulated by Galectin–Glycan Interactions
journal, June 2014


Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

Scaling and assessment of data quality
journal, December 2005

  • Evans, Philip
  • Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
  • DOI: 10.1107/S0907444905036693

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

SWEET - WWW-based rapid 3D construction of oligo- and polysaccharides
journal, September 1999


Carbohydrate Structure Suite (CSS): analysis of carbohydrate 3D structures derived from the PDB
journal, December 2004

  • Lutteke, T.
  • Nucleic Acids Research, Vol. 33, Issue Database issue
  • DOI: 10.1093/nar/gki013

LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions
journal, January 1995

  • Wallace, Andrew C.; Laskowski, Roman A.; Thornton, Janet M.
  • "Protein Engineering, Design and Selection", Vol. 8, Issue 2
  • DOI: 10.1093/protein/8.2.127

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

  • Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
  • Journal of Computational Chemistry, Vol. 25, Issue 13
  • DOI: 10.1002/jcc.20084

Jalview Version 2--a multiple sequence alignment editor and analysis workbench
journal, January 2009


    Works referencing / citing this record:

    “Stuck on sugars – how carbohydrates regulate cell adhesion, recognition, and signaling”
    journal, July 2019


    Glycan recognition in globally dominant human rotaviruses
    journal, July 2018