Journal ArticleDOI
Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency.
Stéphanie Dupuis,Emmanuelle Jouanguy,Sami Al-Hajjar,Claire Fieschi,Ibrahim Al-Mohsen,Suliman Al-Jumaah,Kun Yang,Ariane Chapgier,Celine Eidenschenk,Pierre Eid,Abdulaziz Al Ghonaium,Haysam Tufenkeji,Husn H. Frayha,Suleiman Al-Gazlan,Hassan Al-Rayes,Robert D. Schreiber,Ion Gresser,Jean-Laurent Casanova,Jean-Laurent Casanova +18 more
TLDR
Two unrelated infants homozygous with respect to mutated STAT1 alleles are reported, both infants suffered from mycobacterial disease, but unlike individuals with IFN-γR deficiency, both died of viral disease.Abstract:
The receptors for interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma activate components of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, leading to the formation of at least two transcription factor complexes. STAT1 interacts with STAT2 and p48/IRF-9 to form the transcription factor IFN-stimulated gene factor 3 (ISGF3). STAT1 dimers form gamma-activated factor (GAF). ISGF3 is induced mainly by IFN-alpha/beta, and GAF by IFN-gamma, although both factors can be activated by both types of IFN. Individuals with mutations in either chain of the IFN-gamma receptor (IFN-gammaR) are susceptible to infection with mycobacteria. A heterozygous STAT1 mutation that impairs GAF but not ISGF3 activation has been found in other individuals with mycobacterial disease. No individuals with deleterious mutations in the IFN-alpha/beta signaling pathway have been described. We report here two unrelated infants homozygous with respect to mutated STAT1 alleles. Neither IFN-alpha/beta nor IFN-gamma activated STAT1-containing transcription factors. Like individuals with IFN-gammaR deficiency, both infants suffered from mycobacterial disease, but unlike individuals with IFN-gammaR deficiency, both died of viral disease. Viral multiplication was not inhibited by recombinant IFN-alpha/beta in cell lines from the two individuals. Inherited impairment of the STAT1-dependent response to human IFN-alpha/beta thus results in susceptibility to viral disease.read more
Citations
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Interferon-inducible antiviral effectors
TL;DR: This Review discusses four main effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′,5′-oligoadenylate-synthetase-directed ribonuclease L pathways, the protein kinase R pathway and the ISG15 ubiquitin-like pathway.
Journal ArticleDOI
A diverse range of gene products are effectors of the type I interferon antiviral response
John W. Schoggins,Sam J. Wilson,Maryline Panis,Mary Murphy,Christopher T. Jones,Paul D. Bieniasz,Charles M. Rice +6 more
TL;DR: It is shown that different viruses are targeted by unique sets of ISGs, and that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities.
Journal ArticleDOI
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.
Carly G. K. Ziegler,Samuel J. Allon,Sarah K. Nyquist,Ian M. Mbano,Vincent N. Miao,Constantine N. Tzouanas,Yuming Cao,Ashraf S. Yousif,Julia Bals,Blake M. Hauser,Blake M. Hauser,Jared Feldman,Jared Feldman,Christoph Muus,Christoph Muus,Marc H. Wadsworth,Samuel W. Kazer,Travis K. Hughes,Benjamin Doran,G. James Gatter,G. James Gatter,G. James Gatter,Marko Vukovic,Faith Taliaferro,Faith Taliaferro,Benjamin E. Mead,Zhiru Guo,Jennifer P. Wang,Delphine Gras,Magali Plaisant,Meshal Ansari,Ilias Angelidis,Heiko Adler,Jennifer M.S. Sucre,Chase J. Taylor,Brian M. Lin,Avinash Waghray,Vanessa Mitsialis,Vanessa Mitsialis,Daniel F. Dwyer,Kathleen M. Buchheit,Joshua A. Boyce,Nora A. Barrett,Tanya M. Laidlaw,Shaina L. Carroll,Lucrezia Colonna,Victor Tkachev,Victor Tkachev,Christopher W. Peterson,Christopher W. Peterson,Alison Yu,Alison Yu,Hengqi Betty Zheng,Hengqi Betty Zheng,Hannah P. Gideon,Caylin G. Winchell,Philana Ling Lin,Philana Ling Lin,Colin D. Bingle,Scott B. Snapper,Scott B. Snapper,Jonathan A. Kropski,Jonathan A. Kropski,Fabian J. Theis,Herbert B. Schiller,Laure-Emmanuelle Zaragosi,Pascal Barbry,Alasdair Leslie,Alasdair Leslie,Hans-Peter Kiem,Hans-Peter Kiem,JoAnne L. Flynn,Sarah M. Fortune,Sarah M. Fortune,Sarah M. Fortune,Bonnie Berger,Robert W. Finberg,Leslie S. Kean,Leslie S. Kean,Manuel Garber,Aaron G. Schmidt,Aaron G. Schmidt,Daniel Lingwood,Alex K. Shalek,Jose Ordovas-Montanes,Nicholas E. Banovich,Alvis Brazma,Tushar J. Desai,Thu Elizabeth Duong,Oliver Eickelberg,Christine S. Falk,Michael Farzan,Ian A. Glass,Muzlifah Haniffa,Peter Horvath,Deborah T. Hung,Naftali Kaminski,Mark A. Krasnow,Malte Kühnemund,Robert Lafyatis,Haeock Lee,Sylvie Leroy,Sten Linnarson,Joakim Lundeberg,Kerstin B. Meyer,Alexander V. Misharin,Martijn C. Nawijn,Marko Nikolic,Dana Pe'er,Joseph E. Powell,Stephen R. Quake,Jay Rajagopal,Purushothama Rao Tata,Emma L. Rawlins,Aviv Regev,Paul A. Reyfman,Mauricio Rojas,Orit Rosen,Kourosh Saeb-Parsy,Christos Samakovlis,Herbert B. Schiller,Joachim L. Schultze,Max A. Seibold,Douglas P. Shepherd,Jason R. Spence,Avrum Spira,Xin Sun,Sarah A. Teichmann,Fabian J. Theis,Alexander M. Tsankov,Maarten van den Berge,Michael von Papen,Jeffrey A. Whitsett,Ramnik J. Xavier,Yan Xu,Kun Zhang +135 more
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
Journal ArticleDOI
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Qian Zhang,Paul Bastard,Paul Bastard,Zhiyong Liu,Jérémie Le Pen,Marcela Moncada-Vélez,Jie Chen,Masato Ogishi,Ira K. D. Sabli,Stephanie Hodeib,Cecilia B. Korol,Jérémie Rosain,Jérémie Rosain,Kaya Bilguvar,Junqiang Ye,Alexandre Bolze,Benedetta Bigio,Rui Yang,Andrés Augusto Arias,Andrés Augusto Arias,Qinhua Zhou,Yu Zhang,Fanny Onodi,Sarantis Korniotis,Léa Karpf,Quentin Philippot,Quentin Philippot,Marwa Chbihi,Marwa Chbihi,Lucie Bonnet-Madin,Karim Dorgham,Nikaïa Smith,William M. Schneider,Brandon S. Razooky,Hans-Heinrich Hoffmann,Eleftherios Michailidis,Leen Moens,Ji Eun Han,Lazaro Lorenzo,Lazaro Lorenzo,Lucy Bizien,Lucy Bizien,Philip Meade,Anna-Lena Neehus,Anna-Lena Neehus,Aileen Camille Ugurbil,Aurélien Corneau,Gaspard Kerner,Gaspard Kerner,Peng Zhang,Franck Rapaport,Yoann Seeleuthner,Yoann Seeleuthner,Jeremy Manry,Jeremy Manry,Cécile Masson,Yohann Schmitt,Agatha Schlüter,Tom Le Voyer,Tom Le Voyer,Taushif Khan,Juan Li,Jacques Fellay,Jacques Fellay,Lucie Roussel,Mohammad Shahrooei,Mohammed F. Alosaimi,Davood Mansouri,Haya Al-Saud,Fahd Al-Mulla,Feras M. Almourfi,Saleh Al-Muhsen,Fahad Alsohime,Saeed Al Turki,Rana Hasanato,Diederik van de Beek,Andrea Biondi,Laura Rachele Bettini,Mariella D'Angiò,Paolo Bonfanti,Luisa Imberti,Alessandra Sottini,Simone Paghera,Eugenia Quiros-Roldan,Camillo Rossi,Andrew J. Oler,Miranda F. Tompkins,Camille Alba,Isabelle Vandernoot,Jean-Christophe Goffard,Guillaume Smits,Isabelle Migeotte,Filomeen Haerynck,Pere Soler-Palacín,Andrea Martín-Nalda,Roger Colobran,Pierre-Emmanuel Morange,Sevgi Keles,Fatma Çölkesen,Tayfun Ozcelik,Kadriye Kart Yaşar,Sevtap Şenoğlu,Şemsi Nur Karabela,Carlos Rodríguez-Gallego,Giuseppe Novelli,Sami Hraiech,Yacine Tandjaoui-Lambiotte,Xavier Duval,Xavier Duval,Cédric Laouénan,Cédric Laouénan,Covid-Storm Clinicians§,Covid Clinicians,CoV-Contact Cohort§,CoV-Contact Cohort§,Amsterdam Umc Covid Biobank,Covid Human Genetic Effort,Niaid-Usuhs,Niaid-Usuhs,Niaid-Usuhs,Andrew L. Snow,Clifton L. Dalgard,Joshua D. Milner,Donald C. Vinh,Donald C. Vinh,Trine H. Mogensen,Trine H. Mogensen,Nico Marr,András N Spaan,András N Spaan,András N Spaan,Bertrand Boisson,Bertrand Boisson,Bertrand Boisson,Stéphanie Boisson-Dupuis,Jacinta Bustamante,Jacinta Bustamante,Jacinta Bustamante,Anne Puel,Michael J. Ciancanelli,Isabelle Meyts,Tom Maniatis,Vassili Soumelis,Ali Amara,Ali Amara,Michel C. Nussenzweig,Adolfo García-Sastre,Florian Krammer,Aurora Pujol,Darragh Duffy,Darragh Duffy,Richard P. Lifton,Richard P. Lifton,Richard P. Lifton,Shen-Ying Zhang,Guy Gorochov,Guy Gorochov,Guy Gorochov,Vivien Béziat,Vivien Béziat,Vivien Béziat,Emmanuelle Jouanguy,Vanessa Sancho-Shimizu,Charles M. Rice,Charles M. Rice,Charles M. Rice,Laurent Abel,Luigi D. Notarangelo,Luigi D. Notarangelo,Luigi D. Notarangelo,Aurélie Cobat,Helen C. Su,Jean-Laurent Casanova +172 more
TL;DR: The COVID Human Genetic Effort established to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance finds an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency <0.001.
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Dendritic-cell control of pathogen-driven T-cell polarization.
TL;DR: It is becoming increasingly clear that the selective development of T-cell-polarizing DC subsets is related to the ligation of particular receptors that are involved in DC maturation, and several inconsistencies with this concept remain.
References
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Journal ArticleDOI
How cells respond to interferons
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Journal ArticleDOI
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Journal ArticleDOI
Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway
Marco A Meraz,Marco A Meraz,J. Michael White,Kathleen C. F. Sheehan,Erika A. Bach,Scott J. Rodig,Anand S. Dighe,Daniel H. Kaplan,Joan K. Riley,Andrew C. Greenlund,Dayle Campbell,Karen Carver-Moore,Raymond N. DuBois,Ross G. Clark,Michel Aguet,Michel Aguet,Robert D. Schreiber +16 more
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