The IRE1 arm is the principal UPR arm activated in IAV infection. Activation of this signalling cascade is important for efficient replication of IAV, although the exact mechanism is unclear . Of the myriad responses downstream of IRE1 activation, not all elements are necessarily beneficial to IAV. For instance, upregulation of ERAD-associated mannosidases in IAV infection results in increased HA degradation and hence decreased IAV replication . However, IRE1 can also trigger ER expansion and increased expression of ER chaperones that are beneficial to the virus due to the subsequent increase in the folding efficiency of ER-resident IAV proteins. For instance, folding of HA requires the calnexin chaperone system, including chaperones such as ERp57 which are upregulated in ER stress UPR induces pathogenesis in IAV infection by driving fibrogenesis in lung epithelial cells and is associated with acute lung injury in mice . Rather interestingly, another mechanism by which the UPR impacts disease severity in IAV infection is through XBP1s activation inducing a shift towards oligomannose host N-glycans, with a corresponding increase in mannan-binding lectin-mediated inflammation .