Could UPR Manipulation Help to Tune the Inflammatory Response in the Course of COVID-19?

Authors: Cirone M*

Volume 4, Issue 2

Abstract

Highly pathogenic coronavirus SARS-CoV2, belonging to coronaviridae family, preferentially infects alveolar epithelial cells and immune cells resident or recruited in the lung, causing the disease known as COVID-19. As for other viruses, SARS-CoV2is sensed by several PRRs, particularly TLR3 that triggers an intracellular signaling culminating in activation of transcription factors that promote the release of inflammatory and anti-viral cytokines, deeply shaping immune response. In a subgroup of patents, a massive release of inflammatory cytokines may also occur, strongly contributing to destroy alveolar cells, fibrosis and endothelial injury, thus favoring the activation of coagulation cascade. Viral infection also triggers UPR, an integrated response to stress, by activating the antiviral kinase PKR and by perturbing ER homeostasis. ER stress/UPR strongly contributes to the regulation of cytokine release also because its signaling intersects with PRR signaling at multiple levels. In this perspective we will discuss the possibility to tune the inflammatory/immune response to SARS-CoV2 infection by reducing ER stress, manipulating the different arms of UPR or inducing autophagy.

Keywords: UPR; PRRs; Inflammatory Cytokines; Autophagy; SARS-Cov-2; COVID-19

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