Severe viral respiratory infections in children with IFIH1 loss-of-function mutations

Author:

Asgari Samira12ORCID,Schlapbach Luregn J.345,Anchisi Stéphanie6,Hammer Christian12,Bartha Istvan12,Junier Thomas12,Mottet-Osman Geneviève6,Posfay-Barbe Klara M.7,Longchamp David8,Stocker Martin9,Cordey Samuel10,Kaiser Laurent10,Riedel Thomas5,Kenna Tony11,Long Deborah34,Schibler Andreas34,Telenti Amalio12ORCID,Tapparel Caroline6,McLaren Paul J.1314ORCID,Garcin Dominique6,Fellay Jacques12ORCID

Affiliation:

1. Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland;

2. Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland;

3. Paediatric Critical Care Research Group, Mater Research Institute, University of Queensland, Brisbane, QLD 4101, Australia;

4. Paediatric Intensive Care Unit, Lady Cilento Children’s Hospital, Brisbane, QLD 4101, Australia;

5. Pediatric Intensive Care Unit, Department of Pediatrics, Inselspital, University Children’s Hospital and University of Bern, 3010, Switzerland;

6. Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, 1205, Switzerland;

7. Pediatric Infectious Diseases Unit, Geneva University Hospital, Geneva, 1205, Switzerland;

8. Pediatric Intensive Care Unit, Lausanne University Hospital, Lausanne, 1011, Switzerland;

9. Neonatal and Pediatric Intensive Care Unit, Children's Hospital, Lucerne, 6000, Switzerland;

10. Laboratory of Virology, Division of Infectious Diseases, University of Geneva Medical School, Geneva University Hospitals, Geneva, 1205, Switzerland;

11. Institute for Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD 4000, Australia;

12. J. Craig Venter Institute, La Jolla, CA 92037;

13. National Laboratory for HIV Genetics, JC Wilt Infectious Disease Research Center, Public Health Agency of Canada, Winnipeg, MB R3E 0W3, Canada;

14. Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

Abstract

Significance Life-threatening susceptibility to common respiratory infections in previously healthy children can be indicative of pathogen-specific primary immunodeficiencies due to rare deleterious variants in key genes and pathways of the immune system. These findings have implications for prevention and treatment of susceptible children.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Publisher

Proceedings of the National Academy of Sciences

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