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Temporal changes in sialoglycan binding profile of human H3N2 influenza viruses
datasetposted on 24.08.2020, 08:29 authored by Mengting ZhangMengting Zhang
The human H3N2 influenza viruses was introduced into the human population in 1968 as a novel pandemic virus that emerged through genetic reassortment between human H2N2 and avian influenza virus of H3 subtype. A switch in receptor binding specificity is a critical step for influenza interspecies transmission, as avian influenza viruses typically recognize alpha 2, 3-linked sialiosides while human influenza viruses recognize alpha 2,6-linked sialosides. Further, the receptor binding domain (RBD) that mediates binding to sialosides is located at the head of hemagglutinin (HA) protein and is surrounded by antigenic sites targeted by antibodies. As such, the RBD of H3N2 viruses may continue to evolve under the pressure of host humoral response as well as the need to optimize binding to sialosides that are present in human airway epithelial cells. The development of glycan array platform has enabled us to efficiently assess influenza binding profiles to various glycans. Analyzing the temporal changes of the receptor binding profile of human H3N2 influenza virus will help us to understand viral evolutionary path under the complex selection pressures posed by the host, and if there is any potential evolutionary constrain for these viruses over time.
Here, twenty-three vaccine or vaccine-like strains and 6 animal isolates were examined binding properties using a synthetic glycan microarray. Our results showed dynamic changes in receptor recognition profile and a gradual decline in the number of glycans that can be recognized by human H3N2 influenza viruses from 1975 to 2018. Importantly, four linear glycans (6’SLN, 6’SLN+sulfate, 6’SLN2-L, and 6’SLN3-L) were commonly recognized by H3N2 human influenza viruses from 1975 to 2018, with the recent H3N2 isolates showing an increased binding affinity for the longer linear glycans 6’SLN2-L and 6’SLN3-L. We also compared the glycan binding pattern of 6 pairs of cell-grown and egg-grown human H3N2 isolates. Our results confirmed that the egg-grown viruses showed distinct receptor binding patterns than their cell-grown counterparts due to egg adaptive mutations at residues xxx and xxx that may change HA antigenicity as recently reported.
Glycan microarray may be used as a risk assessment tool for profiling of influenza virus receptor-binding specificity of zoonotic influenza viruses. With the aim for constructing a “Smart Glycan Array”, we also determining the receptor binding profiles of swine and avian influenza viruses of H3N2 subtype. Three swine H3N2 viruses isolated in 2003, 2011, 2018 similarly recognized the four linear glycans as the human H3N2 viruses. Notably, the swine viruses also showed binding for alpha 2,6-linked multi-branched N-glycans that was only recognized by early human H3N2 strains. In contrast, three avian influenza viruses isolated from 2009, 2014, and 2018 showed comparable binding to alpha 2,3-linked sialosides.
In conclusion, these findings suggest a gradual decline in glycan species used by human H3N2 influenza viruses over time. Further investigation on the biological function and the distribution of the four N-linked α2–6-sialosides favored by the human seasonal H3N2 viruses will help us to better define the tropism of human H3N2 viruses at human airway.