The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection
Producción Científica
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Valladolid |
| Repositorio: | UVaDOC. Repositorio Documental de la Universidad de Valladolid |
| OAI Identifier: | oai:uvadoc.uva.es:10324/73859 |
| Acceso en línea: | https://doi.org/10.1016/j.bbadis.2024.167193 https://uvadoc.uva.es/handle/10324/73859 |
| Access Level: | acceso abierto |
| Palabra clave: | Biomedicina COVID-19 Cytokines Fluvoxamine Pneumonia TLR Transcription factors Unfolded protein response Viral sepsis Variants of concern 24 Ciencias de la Vida |
| id |
ES_f8aaaf8669ed8cee7dde8da8e360fcc1 |
|---|---|
| oai_identifier_str |
oai:uvadoc.uva.es:10324/73859 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| dc.title.none.fl_str_mv |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection |
| title |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection |
| spellingShingle |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection Fernández, Jose Javier Biomedicina COVID-19 Cytokines Fluvoxamine Pneumonia TLR Transcription factors Unfolded protein response Viral sepsis Variants of concern 24 Ciencias de la Vida |
| title_short |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection |
| title_full |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection |
| title_fullStr |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection |
| title_full_unstemmed |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection |
| title_sort |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection |
| dc.creator.none.fl_str_mv |
Fernández, Jose Javier Marín, Arturo Rosales, Romel Penrice-Randal, Rebekah Mlcochova, Petra Alvarez, Yolanda Villalón-Letelier, Fernando Yildiz, Soner Pérez, Enrique Rathnasinghe, Raveen Cupic, Anastasija Kehrer, Thomas B Uccellini, Melissa Alonso, Sara Martínez, Fernando Lynn McGovern, Briana J Clark, Jordan Sharma, Parul Bayón Prieto, Yolanda Alonso, Andrés A Albrecht, Randy M White, Kris Schotsaert, Michael Miorin, Lisa P Stewart, James A Hiscox, Julian K Gupta, Ravindra Irigoyen, Nerea García-Sastre, Adolfo Sánchez Crespo, Mariano Fernández, Nieves |
| author |
Fernández, Jose Javier |
| author_facet |
Fernández, Jose Javier Marín, Arturo Rosales, Romel Penrice-Randal, Rebekah Mlcochova, Petra Alvarez, Yolanda Villalón-Letelier, Fernando Yildiz, Soner Pérez, Enrique Rathnasinghe, Raveen Cupic, Anastasija Kehrer, Thomas B Uccellini, Melissa Alonso, Sara Martínez, Fernando Lynn McGovern, Briana J Clark, Jordan Sharma, Parul Bayón Prieto, Yolanda Alonso, Andrés A Albrecht, Randy M White, Kris Schotsaert, Michael Miorin, Lisa P Stewart, James A Hiscox, Julian K Gupta, Ravindra Irigoyen, Nerea García-Sastre, Adolfo Sánchez Crespo, Mariano Fernández, Nieves |
| author_role |
author |
| author2 |
Marín, Arturo Rosales, Romel Penrice-Randal, Rebekah Mlcochova, Petra Alvarez, Yolanda Villalón-Letelier, Fernando Yildiz, Soner Pérez, Enrique Rathnasinghe, Raveen Cupic, Anastasija Kehrer, Thomas B Uccellini, Melissa Alonso, Sara Martínez, Fernando Lynn McGovern, Briana J Clark, Jordan Sharma, Parul Bayón Prieto, Yolanda Alonso, Andrés A Albrecht, Randy M White, Kris Schotsaert, Michael Miorin, Lisa P Stewart, James A Hiscox, Julian K Gupta, Ravindra Irigoyen, Nerea García-Sastre, Adolfo Sánchez Crespo, Mariano Fernández, Nieves |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Biomedicina COVID-19 Cytokines Fluvoxamine Pneumonia TLR Transcription factors Unfolded protein response Viral sepsis Variants of concern 24 Ciencias de la Vida |
| topic |
Biomedicina COVID-19 Cytokines Fluvoxamine Pneumonia TLR Transcription factors Unfolded protein response Viral sepsis Variants of concern 24 Ciencias de la Vida |
| description |
Producción Científica |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://doi.org/10.1016/j.bbadis.2024.167193 https://uvadoc.uva.es/handle/10324/73859 |
| url |
https://doi.org/10.1016/j.bbadis.2024.167193 https://uvadoc.uva.es/handle/10324/73859 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
https://doi.org/10.1016/j.bbadis.2024.167193 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolid instname:Universidad de Valladolid |
| instname_str |
Universidad de Valladolid |
| reponame_str |
UVaDOC. Repositorio Documental de la Universidad de Valladolid |
| collection |
UVaDOC. Repositorio Documental de la Universidad de Valladolid |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869425023226216448 |
| spelling |
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infectionFernández, Jose JavierMarín, ArturoRosales, RomelPenrice-Randal, RebekahMlcochova, PetraAlvarez, YolandaVillalón-Letelier, FernandoYildiz, SonerPérez, EnriqueRathnasinghe, RaveenCupic, AnastasijaKehrer, ThomasB Uccellini, MelissaAlonso, SaraMartínez, FernandoLynn McGovern, BrianaJ Clark, JordanSharma, ParulBayón Prieto, YolandaAlonso, AndrésA Albrecht, RandyM White, KrisSchotsaert, MichaelMiorin, LisaP Stewart, JamesA Hiscox, JulianK Gupta, RavindraIrigoyen, NereaGarcía-Sastre, AdolfoSánchez Crespo, MarianoFernández, NievesBiomedicinaCOVID-19 Cytokines Fluvoxamine Pneumonia TLR Transcription factors Unfolded protein response Viral sepsis Variants of concern24 Ciencias de la VidaProducción CientíficaSARS-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.Junta de Castilla y León/Fondo Social Europeo Grants CSI035P17 and VA175P20Plan Nacional de Salud y Farmacia Grant SAF2017-83079-R and Grant PID2020-113751RB-I00 funded by MCIN/AEI/ 10.13039/501100011033European Commission-NextGenerationEU, (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global)Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA)Fondo COVID-19 del Instituto de Salud Carlos III/Junta de Castilla y LeónU.S. Food and Drug Administration Medical Countermeasures Initiative contract (75F40120C00085)G2P-UK: A national virology consortium to address phenotypic consequences of SARS-CoV-2 genomic variationNational Institutes of Health (NIH) grant: R21AI147172 (N.I.), NIH/NIAID R01AI160706, NIH/NIAID R21AI176069, and NIH/NIDDK R01DK130425This work was also partly supported by NIAID grant U19AI135972, and by CRIPT (Center for Research on Influenza Pathogenesis and Transmission), a NIAID funded Center of Excellence for Influenza Research and Response (CEIRR, contract # 75N93021C00014) (A.G.S.). This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai and supported by the Clinical and Translational Science Awards (CTSA) grant UL1TR004419 from the National Center for Advancing Translational Sciences.Elsevier2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.1016/j.bbadis.2024.167193https://uvadoc.uva.es/handle/10324/73859reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolidinstname:Universidad de ValladolidIngléshttps://doi.org/10.1016/j.bbadis.2024.167193info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:uvadoc.uva.es:10324/738592026-06-13T12:44:47Z |
| score |
15,811543 |