Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency

Vavassori, Stefano and Chou, Janet and Faletti, Laura Eva and Haunerdinger, Veronika and Opitz, Lennart and Joset, Pascal and Fraser, Christopher J. and Prader, Seraina and Gao, Xianfei and Schuch, Luise A. and Wagner, Matias and Hoefele, Julia and Maccari, Maria Elena and Zhu, Ying and Elakis, George and Gabbett, Michael T. and Forstner, Maria and Omran, Heymut and Kaiser, Thomas and Kessler, Christina and Olbrich, Heike and Frosk, Patrick and Almutairi, Abduarahman and Platt, Craig D. and Elkins, Megan and Weeks, Sabrina and Rubin, Tamar and Planas, Raquel and Marchetti, Tommaso and Koovely, Danil and Klämbt, Verena and Soliman, Neveen A. and von Hardenberg, Sandra and Klemann, Christian and Baumann, Ulrich and Lenz, Dominic and Klein-Franke, Andreas and Schwemmle, Martin and Huber, Michael and Sturm, Ekkehard and Hartleif, Steffen and Häffner, Karsten and Gimpel, Charlotte and Brotschi, Barbara and Laube, Guido and Güngör, Tayfun and Buckley, Michael F. and Kottke, Raimund and Staufner, Christian and Hildebrandt, Friedhelm and Reu-Hofer, Simone and Moll, Solange and Weber, Achim and Kaur, Hundeep and Ehl, Stephan and Hiller, Sebastian and Geha, Raif and Roscioli, Tony and Griese, Matthias and Pachlopnik Schmid, Jana. (2021) Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency. The Journal of Allergy & Clinical Immunology, 148 (2). pp. 381-393.

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Official URL: https://edoc.unibas.ch/86552/

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Recognition of viral nucleic acids is one of the primary triggers for a type I interferon-mediated antiviral immune response. Inborn errors of type I interferon immunity can be associated with increased inflammation and/or increased susceptibility to viral infections as a result of dysbalanced interferon production. NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. The role of ZNFX1 in the human immune response is not known.; We studied 15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic lymphohistiocytosis-like disease, early-onset seizures, and renal and lung disease.; Whole exome sequencing was performed on 13 patients from 8 families. We investigated the transcriptome, posttranscriptional regulation of interferon-stimulated genes (ISGs) and predisposition to viral infections in primary cells from patients and controls stimulated with synthetic double-stranded nucleic acids.; Deleterious homozygous and compound heterozygous ZNFX1 variants were identified in all 13 patients. Stimulation of patient-derived primary cells with synthetic double-stranded nucleic acids was associated with a deregulated pattern of expression of ISGs and alterations in the half-life of the mRNA of ISGs and also associated with poorer clearance of viral infections by monocytes.; ZNFX1 is an important regulator of the response to double-stranded nucleic acids stimuli following viral infections. ZNFX1 deficiency predisposes to severe viral infections and a multisystem inflammatory disease.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller)
UniBasel Contributors:Hiller, Sebastian
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Mar 2022 08:24
Deposited On:03 Mar 2022 08:24

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