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

While cytokines that amplify stress may be favorable in the context of halting viral replication, inappropriate or continued activation of this pathway in the absence of overt pathogens in chronic inflammatory diseases perpetuates a cycle of stress and inflammation. 77 This could result in poor barrier function, due to reduced secretion of barrier proteins and diminished epithelial integrity ( Figure 5 ). For example, type I IFNs are essential for clearing viral infection. However, prolonged activation of type I IFNs in chronic infection leads to immune . Virus-controlled UPR response. In homeostatic conditions, proteins are correctly folded in the ER and secreted from cells. However, ER protein misfolding activates UPR pathways leading to the degradation of misfolded proteins, autophagy, inflammation and apoptosis. Viruses can directly or indirectly affect the UPR by selective activation or inhibition of UPR components (shown with red arrows) through endosomal and cytosolic PRRs. Viral-controlled UPR pathways then ultimately boost the production of viral proteins, while dampening the immune response against the virus.