Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection

PLoS Pathog. 2013 Mar;9(3):e1003223. doi: 10.1371/journal.ppat.1003223. Epub 2013 Mar 14.

Abstract

The first step in influenza infection of the human respiratory tract is binding of the virus to sialic (Sia) acid terminated receptors. The binding of different strains of virus for the receptor is determined by the α linkage of the sialic acid to galactose and the adjacent glycan structure. In this study the N- and O-glycan composition of the human lung, bronchus and nasopharynx was characterized by mass spectrometry. Analysis showed that there was a wide spectrum of both Sia α2-3 and α2-6 glycans in the lung and bronchus. This glycan structural data was then utilized in combination with binding data from 4 of the published glycan arrays to assess whether these current glycan arrays were able to predict replication of human, avian and swine viruses in human ex vivo respiratory tract tissues. The most comprehensive array from the Consortium for Functional Glycomics contained the greatest diversity of sialylated glycans, but was not predictive of productive replication in the bronchus and lung. Our findings indicate that more comprehensive but focused arrays need to be developed to investigate influenza virus binding in an assessment of newly emerging influenza viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Birds
  • Bronchi / chemistry
  • Bronchi / virology
  • Cell Line
  • Dogs
  • Galactose / metabolism
  • Glycomics*
  • Humans
  • Influenza A virus / physiology*
  • Influenza, Human / metabolism*
  • Influenza, Human / virology
  • Lung / chemistry
  • Lung / virology
  • Microarray Analysis
  • N-Acetylneuraminic Acid / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / isolation & purification*
  • Receptors, Cell Surface / metabolism
  • Respiratory System / chemistry*
  • Respiratory System / virology
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Swine
  • Viral Tropism
  • Virus Attachment
  • Virus Replication

Substances

  • Polysaccharides
  • Receptors, Cell Surface
  • sialic acid receptor
  • N-Acetylneuraminic Acid
  • Galactose

Grant support

This work was supported by Grant 082098 from the Wellcome Trust (to SMH, AD, and JN): Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/96) and Research Fund for Control of Infectious Disease 10091132 from the Government of the Hong Kong Special Administrative Region. Additional funding was from a grant of the European Commission (FP7- GA258084). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.