globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1704259114
论文题名:
Severe viral respiratory infections in children with IFIH1 loss-of-function mutations
作者: Asgari S.; Schlapbach L.J.; Anchisi S.; Hammer C.; Bartha I.; Junier T.; Mottet-Osman G.; Posfay-Barbe K.M.; Longchamp D.; Stocker M.; Cordey S.; Kaiser L.; Riedel T.; Kenna T.; Long D.; Schibler A.; Telenti A.; Tapparel C.; McLaren P.J.; Garcin D.; Fellay J.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2017
卷: 114, 期:31
起始页码: 8342
结束页码: 8347
语种: 英语
英文关键词: IFIH1 ; Respiratory syncytial virus ; Rhinovirus ; RIG-I-like receptor family severe pediatric infectious disease
Scopus关键词: adenosine triphosphatase ; beta interferon ; DNA ; interferon induced helicase C domain containing protein 1 ; transcriptome ; adenosine triphosphatase ; beta interferon ; IFIH1 protein, human ; interferon induced helicase C domain containing protein 1 ; isoprotein ; antigen recognition ; Article ; bronchiolitis ; child ; childhood disease ; controlled study ; disease severity ; enzyme activity ; female ; frameshift mutation ; gene frequency ; gene identification ; gene sequence ; gene targeting ; human ; Human respiratory syncytial virus ; immune deficiency ; in vitro study ; infant ; intensive care ; loss of function mutation ; major clinical study ; male ; nonhuman ; pediatric intensive care unit ; peripheral blood mononuclear cell ; priority journal ; protein stability ; respiratory syncytial virus infection ; RNA sequence ; stop codon ; viral respiratory tract infection ; virus replication ; whole exome sequencing ; biosynthesis ; genetic predisposition ; genetic variation ; genetics ; immunology ; newborn ; Pneumovirus ; preschool child ; prospective study ; respiratory tract infection ; Rhinovirus ; virology ; Adenosine Triphosphatases ; Child, Preschool ; Critical Care ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Immunologic Deficiency Syndromes ; Infant ; Infant, Newborn ; Interferon-beta ; Interferon-Induced Helicase, IFIH1 ; Male ; Prospective Studies ; Protein Isoforms ; Respiratory Syncytial Viruses ; Respiratory Tract Infections ; Rhinovirus ; Virus Replication
英文摘要: Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated that the resulting proteins are unable to induce IFN-ß, are intrinsically less stable than wild-type IFIH1, and lack ATPase activity. In vitro assays showed that IFIH1 effectively restricts replication of human respiratory syncytial virus and rhinoviruses. We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses.
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163810
Appears in Collections:气候变化与战略

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作者单位: Asgari, S., Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland; Schlapbach, L.J., Paediatric Critical Care Research Group, Mater Research Institute, University of Queensland, Brisbane, QLD 4101, Australia, Paediatric Intensive Care Unit, Lady Cilento Children’s Hospital, Brisbane, QLD 4101, Australia, Pediatric Intensive Care Unit, Department of Pediatrics, Inselspital, University Children’s Hospital, University of Bern, 3010, Switzerland; Anchisi, S., Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, 1205, Switzerland; Hammer, C., Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland; Bartha, I., Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland; Junier, T., Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland; Mottet-Osman, G., Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, 1205, Switzerland; Posfay-Barbe, K.M., Pediatric Infectious Diseases Unit, Geneva University Hospital, Geneva, 1205, Switzerland; Longchamp, D., Pediatric Intensive Care Unit, Lausanne University Hospital, Lausanne, 1011, Switzerland; Stocker, M., Neonatal and Pediatric Intensive Care Unit, Children’s Hospital, Lucerne, 6000, Switzerland; Cordey, S., Laboratory of Virology, Division of Infectious Diseases, University of Geneva Medical School, Geneva University Hospitals, Geneva, 1205, Switzerland; Kaiser, L., Laboratory of Virology, Division of Infectious Diseases, University of Geneva Medical School, Geneva University Hospitals, Geneva, 1205, Switzerland; Riedel, T., Pediatric Intensive Care Unit, Department of Pediatrics, Inselspital, University Children’s Hospital, University of Bern, 3010, Switzerland; Kenna, T., Institute for Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD 4000, Australia; Long, D., Paediatric Critical Care Research Group, Mater Research Institute, University of Queensland, Brisbane, QLD 4101, Australia, Paediatric Intensive Care Unit, Lady Cilento Children’s Hospital, Brisbane, QLD 4101, Australia; Schibler, A., Paediatric Critical Care Research Group, Mater Research Institute, University of Queensland, Brisbane, QLD 4101, Australia, Paediatric Intensive Care Unit, Lady Cilento Children’s Hospital, Brisbane, QLD 4101, Australia; Telenti, A., J. Craig Venter Institute, La Jolla, CA 92037, United States; Tapparel, C., Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, 1205, Switzerland; McLaren, P.J., National Laboratory for HIV Genetics, JC Wilt Infectious Disease Research Center, Public Health Agency of Canada, Winnipeg, MB R3E 0W3, Canada, Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Garcin, D., Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, 1205, Switzerland; Fellay, J., Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland

Recommended Citation:
Asgari S.,Schlapbach L.J.,Anchisi S.,et al. Severe viral respiratory infections in children with IFIH1 loss-of-function mutations[J]. Proceedings of the National Academy of Sciences of the United States of America,2017-01-01,114(31)
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