气候变化领域集成服务门户(CCPortal): Severe viral respiratory infections in children with IFIH1 loss-of-function mutations

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DOI	10.1073/pnas.1704259114
	Severe viral respiratory infections in children with IFIH1 loss-of-function mutations
	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.
发表日期	2017
ISSN	0027-8424
起始页码	8342
结束页码	8347
卷号	114 期号:31
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.
英文关键词	IFIH1; Respiratory syncytial virus; Rhinovirus; RIG-I-like receptor family severe pediatric infectious disease
语种	英语
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
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160607
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, Lausan...
推荐引用方式 GB/T 7714	Asgari S.,Schlapbach L.J.,Anchisi S.,et al. Severe viral respiratory infections in children with IFIH1 loss-of-function mutations[J],2017,114(31).
APA	Asgari S..,Schlapbach L.J..,Anchisi S..,Hammer C..,Bartha I..,...&Fellay J..(2017).Severe viral respiratory infections in children with IFIH1 loss-of-function mutations.Proceedings of the National Academy of Sciences of the United States of America,114(31).
MLA	Asgari S.,et al."Severe viral respiratory infections in children with IFIH1 loss-of-function mutations".Proceedings of the National Academy of Sciences of the United States of America 114.31(2017).