Glycomic Analysis of Human Respiratory Tract Tissues and Correlation with Influenza Virus Infection

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.

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

“…2 Table 2). The pattern of binding to the major analogs of human receptors 6=SL, 6=SLN, and sulfated 6-Su-6=SLN and the surrogate of human receptors Neu5AcBn (30) was identical among all viruses tested ( Table 2 shows Table 2). Interestingly, the mutations at amino acids that we identified as determinants of the antigenic phenotype contributed to the switch in binding affinity.…”

Antigenic and Receptor Binding Properties of Enterovirus 68

“…It was previously reported that a wide range of sialylated O-and N-glycans are extensively expressed on the human airway tract (28). Therefore, it might be possible that our method using trisaccharides failed to detect the differences in binding patterns which are present only in the naturally existing glycans in the human airway tract.…”

Pandemic Swine H1N1 Influenza Viruses with Almost Undetectable Neuraminidase Activity Are Not Transmitted via Aerosols in Ferrets and Are Inhibited by Human Mucus but Not Swine Mucus

“…Interestingly, a previous study showed that an overlay of human mucus on MDCK cell monolayers seemed to be more inhibitory to viruses than an overlay of porcine mucus, despite similar sialic acid content, although this effect showed some strain specificity (20). The porcine and human respiratory glycomes show similarities, including the expression of ␣2,3 and ␣2,6 sialylated glycoproteins and large complex N-glycans with sialylated poly-LacNAc chains, but differences have been characterized (34,35). One difference is that humans express N-acetylneuraminic acid (Neu5Ac) and lack N-glycolylneuraminic acid (Neu5Gc), which is expressed in pigs (36,37).…”