SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells

Nguyen, Long C.; Renner, David M.; Silva, Diane; Yang, Dongbo; Parenti, Nicholas A.; Medina, Kaeri M.; Nicolaescu, Vlad; Gula, Haley; Drayman, Nir; Valdespino, Andrea; Mohamed, Adil; Dann, Christopher; Wannemo, Kristin; Robinson-Mailman, Lydia; Gonzalez, Alan; Stock, Letícia; Cao, Mengrui; Qiao, Zeyu; Moellering, Raymond E.; Tay, Savas; Randall, Glenn; Beers, Michael F.; Rosner, Marsha Rich; Oakes, Scott A.; Weiss, Susan R.

doi:10.1128/mbio.02415-22

SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells

Journal Article · Tue Sep 20 00:00:00 EDT 2022 · mBio (Online)

DOI:https://doi.org/10.1128/mbio.02415-22· OSTI ID:2469989

Nguyen, Long C. ^[1]; Renner, David M. ^[2]; Silva, Diane ^[1]; Yang, Dongbo ^[1]; Parenti, Nicholas A. ^[2]; Medina, Kaeri M. ^[2]; Nicolaescu, Vlad ^[3]; Gula, Haley ^[3]; Drayman, Nir ^[1]; Valdespino, Andrea ^[1]; Mohamed, Adil ^[1]; Dann, Christopher ^[1]; Wannemo, Kristin ^[1]; Robinson-Mailman, Lydia ^[1]; Gonzalez, Alan ^[1]; Stock, Letícia ^[1]; Cao, Mengrui ^[1]; Qiao, Zeyu ^[1]; Moellering, Raymond E. ^[1]; Tay, Savas ^[1] more »

Univ. of Chicago, IL (United States)
Univ. of Pennsylvania, Philadelphia, PA (United States)
Univ. of Chicago, IL (United States); Argonne National Laboratory (ANL), Argonne, IL (United States)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed to be essential for viral replication. We examined the master UPR sensor IRE1α kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1α-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found that human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1α as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1α through autophosphorylation, but its RNase activity fails to splice XBP1. Moreover, while IRE1α was dispensable for replication in human cells for all coronaviruses tested, it was required for maximal expression of genes associated with several key cellular functions, including the interferon signaling pathway, during SARS-CoV-2 infection. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1α, perhaps as a strategy to eliminate detection by the host immune system.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2469989

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 5 Vol. 13; ISSN 2150-7511

Publisher:: American Society for Microbiology (ASM)Copyright Statement

Country of Publication:: United States

Language:: English

References (75)

Coronaviruses: An Overview of Their Replication and Pathogenesis Fehr, Anthony R.; Perlman, Stanley Coronaviruses https://doi.org/10.1007/978-1-4939-2438-7_1	book	January 2015
Modulation of the unfolded protein response impedes tumor cell adaptation to proteotoxic stress: a PERK for hepatocellular carcinoma therapy Vandewynckel, Yves-Paul; Laukens, Debby; Bogaerts, Eliene Hepatology International, Vol. 9, Issue 1 https://doi.org/10.1007/s12072-014-9582-0	journal	October 2014
Functional and Genomic Analyses Reveal an Essential Coordination between the Unfolded Protein Response and ER-Associated Degradation Travers, Kevin J.; Patil, Christopher K.; Wodicka, Lisa Cell, Vol. 101, Issue 3 https://doi.org/10.1016/S0092-8674(00)80835-1	journal	April 2000
XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor Yoshida, Hiderou; Matsui, Toshie; Yamamoto, Akira Cell, Vol. 107, Issue 7 https://doi.org/10.1016/S0092-8674(01)00611-0	journal	December 2001
Multiple ways to die: Delineation of the unfolded protein response and apoptosis induced by Surfactant Protein C BRICHOS mutants Maguire, Jean Ann; Mulugeta, Surafel; Beers, Michael F. The International Journal of Biochemistry & Cell Biology, Vol. 44, Issue 1 https://doi.org/10.1016/j.biocel.2011.10.003	journal	January 2012
IRE1α Kinase Activation Modes Control Alternate Endoribonuclease Outputs to Determine Divergent Cell Fates Han, Dan; Lerner, Alana G.; Vande Walle, Lieselotte Cell, Vol. 138, Issue 3 https://doi.org/10.1016/j.cell.2009.07.017	journal	August 2009
Allosteric Inhibition of the IRE1α RNase Preserves Cell Viability and Function during Endoplasmic Reticulum Stress Ghosh, Rajarshi; Wang, Likun; Wang, Eric S. Cell, Vol. 158, Issue 3 https://doi.org/10.1016/j.cell.2014.07.002	journal	July 2014
Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19 Blanco-Melo, Daniel; Nilsson-Payant, Benjamin E.; Liu, Wen-Chun Cell, Vol. 181, Issue 5 https://doi.org/10.1016/j.cell.2020.04.026	journal	May 2020
Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology Zhao, Ling; Jha, Babal K.; Wu, Ashley Cell Host & Microbe, Vol. 11, Issue 6 https://doi.org/10.1016/j.chom.2012.04.011	journal	June 2012
TLR7-mediated activation of XBP1 correlates with the IFNα production in humans Beisel, Claudia; Ziegler, Susanne; Martrus Zapater, Glòria Cytokine, Vol. 94 https://doi.org/10.1016/j.cyto.2017.04.006	journal	June 2017
Coordination between Two Branches of the Unfolded Protein Response Determines Apoptotic Cell Fate Chang, Tsun-Kai; Lawrence, David A.; Lu, Min Molecular Cell, Vol. 71, Issue 4 https://doi.org/10.1016/j.molcel.2018.06.038	journal	August 2018
A human coronavirus OC43 variant harboring persistence-associated mutations in the S glycoprotein differentially induces the unfolded protein response in human neurons as compared to wild-type virus Favreau, Dominique J.; Desforges, Marc; St-Jean, Julien R. Virology, Vol. 395, Issue 2 https://doi.org/10.1016/j.virol.2009.09.026	journal	December 2009
Nidovirales: Evolving the largest RNA virus genome Gorbalenya, Alexander E.; Enjuanes, Luis; Ziebuhr, John Virus Research, Vol. 117, Issue 1 https://doi.org/10.1016/j.virusres.2006.01.017	journal	April 2006
Coronavirus-induced ER stress response and its involvement in regulation of coronavirus–host interactions Fung, To Sing; Huang, Mei; Liu, Ding Xiang Virus Research, Vol. 194 https://doi.org/10.1016/j.virusres.2014.09.016	journal	December 2014
The ORF8 protein of SARS-CoV-2 induced endoplasmic reticulum stress and mediated immune evasion by antagonizing production of interferon beta Rashid, Farooq; Dzakah, Emmanuel Enoch; Wang, Haiying Virus Research, Vol. 296 https://doi.org/10.1016/j.virusres.2021.198350	journal	April 2021
IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA Calfon, Marcella; Zeng, Huiqing; Urano, Fumihiko Nature, Vol. 415, Issue 6867 https://doi.org/10.1038/415092a	journal	January 2002
Integrative genomics viewer Robinson, James T.; Thorvaldsdóttir, Helga; Winckler, Wendy Nature Biotechnology, Vol. 29, Issue 1 https://doi.org/10.1038/nbt.1754	journal	January 2011
The unfolded protein response: controlling cell fate decisions under ER stress and beyond Hetz, Claudio Nature Reviews Molecular Cell Biology, Vol. 13, Issue 2 https://doi.org/10.1038/nrm3270	journal	January 2012
Metascape provides a biologist-oriented resource for the analysis of systems-level datasets Zhou, Yingyao; Zhou, Bin; Pache, Lars Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-09234-6	journal	April 2019
Viral priming of cell intrinsic innate antiviral signaling by the unfolded protein response Carletti, Tea; Zakaria, Mohammad Khalid; Faoro, Valentina Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-11663-2	journal	August 2019
A molecular single-cell lung atlas of lethal COVID-19 Melms, Johannes C.; Biermann, Jana; Huang, Huachao Nature, Vol. 595, Issue 7865 https://doi.org/10.1038/s41586-021-03569-1	journal	April 2021
Derivation of self-renewing lung alveolar epithelial type II cells from human pluripotent stem cells Jacob, Anjali; Vedaie, Marall; Roberts, David A. Nature Protocols, Vol. 14, Issue 12 https://doi.org/10.1038/s41596-019-0220-0	journal	November 2019
Viruses, endoplasmic reticulum stress, and interferon responses He, B. Cell Death & Differentiation, Vol. 13, Issue 3 https://doi.org/10.1038/sj.cdd.4401833	journal	January 2006
Middle East Respiratory Syndrome Arabi, Yaseen M.; Balkhy, Hanan H.; Hayden, Frederick G. New England Journal of Medicine, Vol. 376, Issue 6 https://doi.org/10.1056/NEJMsr1408795	journal	February 2017
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles Subramanian, A.; Tamayo, P.; Mootha, V. K. Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550 https://doi.org/10.1073/pnas.0506580102	journal	September 2005
Mammalian endoplasmic reticulum stress sensor IRE1 signals by dynamic clustering Li, H.; Korennykh, A. V.; Behrman, S. L. Proceedings of the National Academy of Sciences, Vol. 107, Issue 37 https://doi.org/10.1073/pnas.1010580107	journal	August 2010
SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes Li, Yize; Renner, David M.; Comar, Courtney E. Proceedings of the National Academy of Sciences, Vol. 118, Issue 16 https://doi.org/10.1073/pnas.2022643118	journal	April 2021
MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells Comar, Courtney E.; Otter, Clayton J.; Pfannenstiel, Jessica Proceedings of the National Academy of Sciences, Vol. 119, Issue 21 https://doi.org/10.1073/pnas.2123208119	journal	May 2022
Role of Spike Protein Endodomains in Regulating Coronavirus Entry Shulla, Ana; Gallagher, Tom Journal of Biological Chemistry, Vol. 284, Issue 47 https://doi.org/10.1074/jbc.M109.043547	journal	November 2009
Influenza A Viral Replication Is Blocked by Inhibition of the Inositol-requiring Enzyme 1 (IRE1) Stress Pathway Hassan, Ihab H.; Zhang, Michael S.; Powers, Linda S. Journal of Biological Chemistry, Vol. 287, Issue 7 https://doi.org/10.1074/jbc.M111.284695	journal	February 2012
ER stress signaling has an activating transcription factor 6α (ATF6)-dependent “off-switch” Walter, Franziska; O'Brien, Aisling; Concannon, Caoimhín G. Journal of Biological Chemistry, Vol. 293, Issue 47 https://doi.org/10.1074/jbc.RA118.002121	journal	November 2018
New Insights into the Role of RNase L in Innate Immunity Chakrabarti, Arindam; Jha, Babal Kant; Silverman, Robert H. Journal of Interferon & Cytokine Research, Vol. 31, Issue 1 https://doi.org/10.1089/jir.2010.0120	journal	January 2011
STAR: ultrafast universal RNA-seq aligner Dobin, Alexander; Davis, Carrie A.; Schlesinger, Felix Bioinformatics, Vol. 29, Issue 1 https://doi.org/10.1093/bioinformatics/bts635	journal	October 2012
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features Liao, Y.; Smyth, G. K.; Shi, W. Bioinformatics, Vol. 30, Issue 7 https://doi.org/10.1093/bioinformatics/btt656	journal	November 2013
Interferons, interferon-like cytokines, and their receptors Pestka, Sidney; Krause, Christopher D.; Walter, Mark R. Immunological Reviews, Vol. 202, Issue 1 https://doi.org/10.1111/j.0105-2896.2004.00204.x	journal	December 2004
Interferon signalling network in innate defence Takaoka, Akinori; Yanai, Hideyuki Cellular Microbiology, Vol. 8, Issue 6 https://doi.org/10.1111/j.1462-5822.2006.00716.x	journal	June 2006
Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity Chu, Hin; Shuai, Huiping; Hou, Yuxin Science Advances, Vol. 7, Issue 25 https://doi.org/10.1126/sciadv.abf8577	journal	June 2021
Decay of Endoplasmic Reticulum-Localized mRNAs During the Unfolded Protein Response Hollien, Julie; Weissman, Jonathan S. Science, Vol. 313, Issue 5783 https://doi.org/10.1126/science.1129631	journal	July 2006
IRE1α Cleaves Select microRNAs During ER Stress to Derepress Translation of Proapoptotic Caspase-2 Upton, John-Paul; Wang, Likun; Han, Dan Science, Vol. 338, Issue 6108 https://doi.org/10.1126/science.1226191	journal	November 2012
Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1 Urano, F. Science, Vol. 287, Issue 5453 https://doi.org/10.1126/science.287.5453.664	journal	January 2000
Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2 Drayman, Nir; DeMarco, Jennifer K.; Jones, Krysten A. Science, Vol. 373, Issue 6557 https://doi.org/10.1126/science.abg5827	journal	August 2021
Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 D’Agnillo, Felice; Walters, Kathie-Anne; Xiao, Yongli Science Translational Medicine, Vol. 13, Issue 620 https://doi.org/10.1126/scitranslmed.abj7790	journal	November 2021
Coronavirus Infection Modulates the Unfolded Protein Response and Mediates Sustained Translational Repression Bechill, John; Chen, Zhongbin; Brewer, Joseph W. Journal of Virology, Vol. 82, Issue 9 https://doi.org/10.1128/JVI.00017-08	journal	May 2008
Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages Volk, Aaron; Hackbart, Matthew; Deng, Xufang Journal of Virology, Vol. 94, Issue 11 https://doi.org/10.1128/JVI.00178-20	journal	May 2020
Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Chan, Ching-Ping; Siu, Kam-Leung; Chin, King-Tung Journal of Virology, Vol. 80, Issue 18 https://doi.org/10.1128/JVI.00659-06	journal	September 2006
A Kinome-Wide Small Interfering RNA Screen Identifies Proviral and Antiviral Host Factors in Severe Acute Respiratory Syndrome Coronavirus Replication, Including Double-Stranded RNA-Activated Protein Kinase and Early Secretory Pathway Proteins de Wilde, Adriaan H.; Wannee, Kazimier F.; Scholte, Florine E. M. Journal of Virology, Vol. 89, Issue 16 https://doi.org/10.1128/JVI.01029-15	journal	August 2015
Alphacoronavirus Protein 7 Modulates Host Innate Immune Response Cruz, Jazmina L. G.; Becares, Martina; Sola, Isabel Journal of Virology, Vol. 87, Issue 17 https://doi.org/10.1128/JVI.01032-13	journal	September 2013
The Endoplasmic Reticulum Stress Sensor IRE1α Protects Cells from Apoptosis Induced by the Coronavirus Infectious Bronchitis Virus Fung, To Sing; Liao, Ying; Liu, Ding Xiang Journal of Virology, Vol. 88, Issue 21 https://doi.org/10.1128/JVI.02138-14	journal	November 2014
Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L Goldstein, Stephen A.; Thornbrough, Joshua M.; Zhang, Rong Journal of Virology, Vol. 91, Issue 5 https://doi.org/10.1128/JVI.02201-16	journal	March 2017
Severe Acute Respiratory Syndrome Coronavirus Protein 6 Is Required for Optimal Replication Zhao, Jincun; Falcón, Ana; Zhou, Haixia Journal of Virology, Vol. 83, Issue 5 https://doi.org/10.1128/JVI.02371-08	journal	December 2008
Fusion-defective mutants of mouse hepatitis virus A59 contain a mutation in the spike protein cleavage signal Gombold, J. L.; Hingley, S. T.; Weiss, S. R. Journal of Virology, Vol. 67, Issue 8 https://doi.org/10.1128/JVI.67.8.4504-4512.1993	journal	August 1993
XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response Lee, Ann-Hwee; Iwakoshi, Neal N.; Glimcher, Laurie H. Molecular and Cellular Biology, Vol. 23, Issue 21 https://doi.org/10.1128/MCB.23.21.7448-7459.2003	journal	November 2003
Antagonism of dsRNA-Induced Innate Immune Pathways by NS4a and NS4b Accessory Proteins during MERS Coronavirus Infection Comar, Courtney E.; Goldstein, Stephen A.; Li, Yize mBio, Vol. 10, Issue 2 https://doi.org/10.1128/mBio.00319-19	journal	March 2019
Unfolded Protein Response Inhibition Reduces Middle East Respiratory Syndrome Coronavirus-Induced Acute Lung Injury Sims, Amy C.; Mitchell, Hugh D.; Gralinski, Lisa E. mBio, Vol. 12, Issue 4 https://doi.org/10.1128/mBio.01572-21	journal	August 2021
Respiratory epithelial cell responses to SARS-CoV-2 in COVID-19 Bridges, James P.; Vladar, Eszter K.; Huang, Hua Thorax, Vol. 77, Issue 2 https://doi.org/10.1136/thoraxjnl-2021-217561	journal	August 2021
Transcriptional and Translational Control in the Mammalian Unfolded Protein Response Harding, Heather P.; Calfon, Marcella; Urano, Fumihiko Annual Review of Cell and Developmental Biology, Vol. 18, Issue 1 https://doi.org/10.1146/annurev.cellbio.18.011402.160624	journal	November 2002
The Unfolded Protein Response: Integrating Stress Signals Through the Stress Sensor IRE1α Hetz, Claudio; Martinon, Fabio; Rodriguez, Diego Physiological Reviews, Vol. 91, Issue 4 https://doi.org/10.1152/physrev.00001.2011	journal	October 2011
Parallel Signaling through IRE1α and PERK Regulates Pancreatic Neuroendocrine Tumor Growth and Survival Moore, Paul C.; Qi, Jenny Y.; Thamsen, Maike Cancer Research, Vol. 79, Issue 24 https://doi.org/10.1158/0008-5472.CAN-19-1116	journal	December 2019
Innate Immune Evasion by Human Respiratory RNA Viruses Kikkert, Marjolein Journal of Innate Immunity, Vol. 12, Issue 1 https://doi.org/10.1159/000503030	journal	October 2019
Contributions of alveolar epithelial cell quality control to pulmonary fibrosis Katzen, Jeremy; Beers, Michael F. Journal of Clinical Investigation, Vol. 130, Issue 10 https://doi.org/10.1172/JCI139519	journal	September 2020
A SFTPC BRICHOS mutant links epithelial ER stress and spontaneous lung fibrosis Katzen, Jeremy; Wagner, Brandie D.; Venosa, Alessandro JCI Insight https://doi.org/10.1172/jci.insight.126125	journal	February 2019
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Love, Michael I.; Huber, Wolfgang; Anders, Simon Genome Biology, Vol. 15, Issue 12 https://doi.org/10.1186/s13059-014-0550-8	journal	December 2014
Identification and Implantation Stage-Specific Expression of an Interferon-α-Regulated Gene in Human and Rat Endometrium* Li, Quanxi; Zhang, Meilin; Kumar, Sushma Endocrinology, Vol. 142, Issue 6 https://doi.org/10.1210/endo.142.6.8101	journal	June 2001
The unfolded protein response Zhang, Kezhong; Kaufman, Randal J. Neurology, Vol. 66, Issue 1_suppl_1 https://doi.org/10.1212/01.wnl.0000192306.98198.ec	journal	January 2006
Real-time PCR quantification of spliced X-box binding protein 1 (XBP1) using a universal primer method Yoon, Seung-Bin; Park, Young-Ho; Choi, Seon-A PLOS ONE, Vol. 14, Issue 7 https://doi.org/10.1371/journal.pone.0219978	journal	July 2019
Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Regulates Cell Stress Response and Apoptosis DeDiego, Marta L.; Nieto-Torres, Jose L.; Jiménez-Guardeño, Jose M. PLoS Pathogens, Vol. 7, Issue 10 https://doi.org/10.1371/journal.ppat.1002315	journal	October 2011
Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses Rabouw, Huib H.; Langereis, Martijn A.; Knaap, Robert C. M. PLOS Pathogens, Vol. 12, Issue 10 https://doi.org/10.1371/journal.ppat.1005982	journal	October 2016
Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection Echavarría-Consuegra, Liliana; Cook, Georgia M.; Busnadiego, Idoia PLOS Pathogens, Vol. 17, Issue 6 https://doi.org/10.1371/journal.ppat.1009644	journal	June 2021
In vitrostudy of aldose reductase inhibitor concentrations in the lens and inhibitory effect on sugar alcohol accumulation Yamamoto, Yujiro; Ohtori, Akira Current Eye Research, Vol. 9, Issue 5 https://doi.org/10.3109/02713689008999607	journal	January 1990
Studies With Human Coronaviruses II. Some Properties of Strains 229E and OC43 Bucknall, R. A.; King, L. M.; Kapikian, A. Z. Experimental Biology and Medicine, Vol. 139, Issue 3 https://doi.org/10.3181/00379727-139-36224	journal	March 1972
The Unfolded Protein Response and Autophagy on the Crossroads of Coronaviruses Infections Prestes, Elisa B.; Bruno, Julia C. P.; Travassos, Leonardo H. Frontiers in Cellular and Infection Microbiology, Vol. 11 https://doi.org/10.3389/fcimb.2021.668034	journal	April 2021
Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity Smith, Judith A. Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.00422	journal	March 2018
Coronavirus infection, ER stress, apoptosis and innate immunity Fung, To S.; Liu, Ding X. Frontiers in Microbiology, Vol. 5 https://doi.org/10.3389/fmicb.2014.00296	journal	June 2014
Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1 Adams, Christopher J.; Kopp, Megan C.; Larburu, Natacha Frontiers in Molecular Biosciences, Vol. 6 https://doi.org/10.3389/fmolb.2019.00011	journal	March 2019
XBP-1 Couples Endoplasmic Reticulum Stress to Augmented IFN-β Induction via a cis-Acting Enhancer in Macrophages Zeng, Ling; Liu, Yi-Ping; Sha, Haibo The Journal of Immunology, Vol. 185, Issue 4 https://doi.org/10.4049/jimmunol.0903052	journal	August 2010

Similar Records

3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice

Journal Article · Wed Aug 19 00:00:00 EDT 2020 · Science Translational Medicine · OSTI ID:1661001

Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

Journal Article · Thu Jan 28 23:00:00 EST 2016 · Biochemical and Biophysical Research Communications · OSTI ID:22594209

Masitinib is a Broad Coronavirus 3CL Inhibitor that Blocks Replication of SARS-CoV-2

Journal Article · Thu Aug 19 00:00:00 EDT 2021 · Science · OSTI ID:1819318

Related Subjects

60 APPLIED LIFE SCIENCES
IRE1α pathway
MERS-CoV
OC43
SARS-CoV-2
coronavirus
unfolded protein response

SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells

Citation Formats

References (75)

Similar Records

Related Subjects