Integrated Omics of Influenza A Virus: Correlating Glycan Macro and Micro-heterogeneity with Virus Evolution and Interactions with Host Immune System

摘要

Despite considerable effort, a clear understanding of the relationship between glycosylation of surface protein hemagglutinin (HA) and influenza A virus (IAV) pathogenicity has yet to emerge. HA is known to be heavily glycosylated with between 5 and 12 N-glycosylation sites (sequons). Typically, low sequon number of HA head subunit is linked with high virulence of pandemic strains. As the virus circulates in host populations, the number of sequons on HA head domain increases as a mechanism to evade host adaptive immune response. We performed integrated omics on IAV strains along with glycan array and lectin binding analyses to study how selection pressures drive changes in HA glycosylation, thereby modulating viral fitness and recognition by lectins of the innate immune system.