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

Better understanding of the contribution of ER stress-associated UPR response in viral infection process, temporal sequence of events and pathways to initiation of chronic inflammation and tissue damage is imperative. Understanding how immune responses and inflammatory cytokines regulate UPR in viral infection is crucial, because boosting this physiological process via cytokines could open the way to novel approaches to limit viral replication and acute disease, and rescue individuals with persistent inflammation and associated tissue damage. Clearly, the UPR is intimately involved in viral replication: manipulating ER stress and UPR signalling could potentially limit viral replication and attenuate acute viral infections. Reduction in epithelial cell UPR activation in chronic disease provides an opportunity to limit persistent mucosal inflammation and the extent of tissue damage. The timing and nature of the cytokine response dictate time taken for both viral clearance and restoration of mucosal integrity and homeostasis. Manipulation of cytokine-induced epithelial cell ER stress gives us a chance to tip this fine balance in favor of health rather than disease.