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

Nat Commun. 2015 Sep 30;6:8346. doi: 10.1038/ncomms9346.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cattle Diseases / metabolism
  • Cattle Diseases / virology*
  • Gastroenteritis / metabolism
  • Gastroenteritis / virology
  • Humans
  • Polysaccharides / chemistry*
  • Polysaccharides / metabolism
  • Reassortant Viruses / chemistry
  • Reassortant Viruses / genetics
  • Reassortant Viruses / metabolism*
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism
  • Rotavirus / chemistry
  • Rotavirus / genetics
  • Rotavirus / metabolism*
  • Rotavirus Infections / metabolism*
  • Rotavirus Infections / veterinary*
  • Rotavirus Infections / virology
  • Species Specificity
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism

Substances

  • Polysaccharides
  • Receptors, Virus
  • Viral Nonstructural Proteins

Associated data

  • PDB/4YFW
  • PDB/4YFZ
  • PDB/4YG0
  • PDB/4YG3
  • PDB/4YG6