An absence of glycosylation sites in the globular head domain can reduce calnexin or calreticulin binding at parts of the protein whose folding relies on chaperones, such as near disulfide bonds, and subsequently increase aggregation of misfolded proteins . Absence of glycosylation in the globular head is typical of pandemic influenza strains that arise from zoonotic spillover; the less severe, seasonal strains often acquire mutations in HA that increase the number of glycosylation sites . Although certainly not the only factor, increased activation of the UPR is partially responsible for the increased pathogenesis observed in pandemic strains of IAV . Critically however, extensive glycosylation of HA has long been associated with IAV virulence due to its additional effects on receptor binding, fusion, cleavage, and immune evasion , as well as increased collectin binding and hence virus neutralisation . The exact extent to which differential activation of the UPR due to changes in HA glycosylation impacts pathogenesis remains unclear.