Respiratory viruses employ several strategies to combat host immune responses, and the UPR is no exception . Transcriptomic and proteomic profiling of the UPR in infection have revealed varied host ER stress responses. Infection with most common respiratory viruses results in increased expression of ER stress response genes and proteins , an observation that can be made directly in diseased patients . Importantly, many respiratory viral infections elicit a non-canonical UPR by only activating a subset of the three UPR arms . For example, RSV and IAV infections induce preferential activation of IRE1 and ATF6, but not PERK, although IAV may also induce IRE1 alone or all three arms depending on infection conditions . UPR activation by respiratory viruses is likely somewhat cell-type specific. An example of this is observed in the atypical activation of PERK in RSV infected dendritic cells . Non-canonical UPR activation strongly suggests that the UPR is specifically modulated by viruses. Of the numerous responses mediated by the UPR, some are generally detrimental to viral replication (i.e., viral protein translation inhibition, ERAD), whilst others may advantage the virus (i.e. ER expansion, chaperone expression). Rather unsurprisingly, there are therefore many mechanisms by which respiratory viruses are able to selectively induce or supress elements of the UPR . These mechanisms include surface glycoproteins processed in high volume within the ER, viral ion channels, non-structural and accessory proteins, as well as various stress responses associated with infection.