ER Stress, UPR Activation and the Inflammatory Response to Viral Infection.

Mara Cirone

doi:10.3390/v13050798

Abstract

The response to invading pathogens such as viruses is orchestrated by pattern recognition receptor (PRR) and unfolded protein response (UPR) signaling, which intersects and converges in the activation of proinflammatory pathways and the release of cytokines and chemokines that harness the immune system in the attempt to clear microbial infection. Despite this protective intent, the inflammatory response, particularly during viral infection, may be too intense or last for too long, whereby it becomes the cause of organ or systemic diseases itself. This suggests that a better understanding of the mechanisms that regulate this complex process is needed in order to achieve better control of the side effects that inflammation may cause while potentiating its protective role. The use of specific inhibitors of the UPR sensors or PRRs or the downstream pathways activated by their signaling could offer the opportunity to reach this goal and improve the outcome of inflammation-based diseases associated with viral infections.

Highlights

The response to invading pathogens such as viruses is orchestrated by pattern recognition receptor (PRR) and unfolded protein response (UPR) signaling, which intersects and converges in the activation of proinflammatory pathways and the release of cytokines and chemokines that harness the immune system in the attempt to clear microbial infection
Viruses entering into target cells are promptly recognized by different classes of molecules identified as PRRs, which are mainly represented by the family of Toll-like receptors, nucleoside-binding oligomerization domain containing-like receptors (NLRs), C-type lectin receptors (CRLs), and the cGAS/STING pathway [1,2]
Inflammation in Response to Viral Infection when reactivating from latency in immune-compromised patients, infect epithelial cells, such as alveolar or bronchial cells, as well as endothelial and immune cells, leading to a such as Epstein–Barr virus (EBV) or human cytomegalovirus (HCMV), when reactivating massive proinflammatory cytokine release, known as “cytokine storm syndrome” [29]