Immune regulation of the unfolded protein response at the mucosal barrier in viral infection

Wang, Ran; Moniruzzaman, Md.; Shuffle, Eric; Lourie, Rohan; Hasnain, Sumaira Z

dysfunction and exacerbated tissue damage in the respiratory tract. 77, 78 A careful balance is required; inducing ER stress and UPR pathways will limit viral replication and promote viral clearance in acute infection. However, prolonged ER stress and UPR activation is detrimental to Figure 5 . Proposed mechanism of anti-viral function of cytokines. Pre-infection: Basal level of UPR maintains the homeostasis of secretory cell function. Infection: Host ER stress and UPR are intrinsic mechanisms that will limit viral protein synthesis. However, viruses can potentially bypass these mechanisms to replicate. Specific cytokines (such as type I IFNs) that induce oxidative stress would lead to protein misfolding which will be beneficial in limiting viral infection. Post-infection: Following viral clearance, the wound healing pathways are activated. Specific cytokines, such as IL-10, known to suppress UPR signals and ER stress, will allow the restoration of normal protein production in the cells.