RT info:eu-repo/semantics/article
T1 The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection
A1 Fernández, Jose Javier
A1 Marín, Arturo
A1 Rosales, Romel
A1 Penrice-Randal, Rebekah
A1 Mlcochova, Petra
A1 Alvarez, Yolanda
A1 Villalón-Letelier, Fernando
A1 Yildiz, Soner
A1 Pérez, Enrique
A1 Rathnasinghe, Raveen
A1 Cupic, Anastasija
A1 Kehrer, Thomas
A1 B Uccellini, Melissa
A1 Alonso, Sara
A1 Martínez, Fernando
A1 Lynn McGovern, Briana
A1 J Clark, Jordan
A1 Sharma, Parul
A1 Bayón Prieto, Yolanda
A1 Alonso, Andrés
A1 A Albrecht, Randy
A1 M White, Kris
A1 Schotsaert, Michael
A1 Miorin, Lisa
A1 P Stewart, James
A1 A Hiscox, Julian
A1 K Gupta, Ravindra
A1 Irigoyen, Nerea
A1 García-Sastre, Adolfo
A1 Sánchez Crespo, Mariano
A1 Fernández, Nieves
K1 Biomedicina
K1 COVID-19 Cytokines Fluvoxamine Pneumonia TLR Transcription factors Unfolded protein response Viral sepsis Variants of concern
K1 24 Ciencias de la Vida
AB SARS-CoV-2 infection can cause severe pneumonia, wherein exacerbated inflammation plays a major role. This is reminiscent of the process commonly termed cytokine storm, a condition dependent on a disproportionated production of cytokines. This state involves the activation of the innate immune response by viral patterns and coincides with the biosynthesis of the biomass required for viral replication, which may overwhelm the capacity of the endoplasmic reticulum and drive the unfolded protein response (UPR). The UPR is a signal transduction pathway composed of three branches that is initiated by a set of sensors: inositol-requiring protein 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6). These sensors control adaptive processes, including the transcriptional regulation of proinflammatory cytokines. Based on this background, the role of the UPR in SARS-CoV-2 replication and the ensuing inflammatory response was investigated using in vivo and in vitro models of infection. Mice and Syrian hamsters infected with SARS-CoV-2 showed a sole activation of the Ire1α-Xbp1 arm of the UPR associated with a robust production of proinflammatory cytokines. Human lung epithelial cells showed the dependence of viral replication on the expression of UPR-target proteins branching on the IRE1α-XBP1 arm and to a lower extent on the PERK route. Likewise, activation of the IRE1α-XBP1 branch by Spike (S) proteins from different variants of concern was a uniform finding. These results show that the IRE1α-XBP1 system enhances viral replication and cytokine expression and may represent a potential therapeutic target in SARS-CoV-2 severe pneumonia.
PB Elsevier
YR 2024
FD 2024
LK https://uvadoc.uva.es/handle/10324/73859
UL https://uvadoc.uva.es/handle/10324/73859
LA eng
NO Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Volume 1870, Issue 5, June 2024, 167193
NO Producción Científica
DS UVaDOC
RD 05-feb-2025