DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.

Autor:	Lee S; Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.; Department of Medical Consilience, Graduate School, Dankook University, Yongin-si, South Korea., Zhang Y; Laboratory of Clinical Immunology and Microbiology, Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Newhams M; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Novak T; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.; Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA., Thomas PG; Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA., Mourani PM; Section of Critical Care Medicine, Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Research Institute, Little Rock, Arkansas, USA., Hall MW; Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA., Loftis LL; Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA., Cvijanovich NZ; Division of Critical Care Medicine, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA., Tarquinio KM; Division of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA., Schwarz AJ; Department of Pediatrics, Children's Hospital of Orange County, Orange, California, USA., Weiss SL; Division of Critical Care, Department of Anesthesiology and Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Thomas NJ; Department of Pediatrics, Penn State Hershey Children's Hospital, Penn State University College of Medicine, Hershey, Pennsylvania, USA., Markovitz B; Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, California, USA., Cullimore ML; Division of Pediatric Critical Care, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA., Sanders RC; Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock, Arkansas, USA., Zinter MS; Divisions of Critical Care Medicine and Allergy, Immunology, and Bone Marrow Transplant, Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA., Sullivan JE; Division of Pediatric Critical Care, University of Louisville School of Medicine and Norton Children's Hospital, Louisville, Kentucky, USA., Halasa NB; Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Bembea MM; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Giuliano JS; Division of Critical Care, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA., Typpo KV; Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, Arizona, USA., Nofziger RA; Division of Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio, USA., Shein SL; Division of Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA., Kong M; Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Coates BM; Division of Critical Care Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Weiss ST; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lange C; Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Su HC; Laboratory of Clinical Immunology and Microbiology, Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Randolph AG; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.; Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA.; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2022 Nov 28; Vol. 226 (11), pp. 2030-2036.
DOI:	10.1093/infdis/jiac350
Abstrakt:	Background: Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children. Methods: We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score. Results: Common variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity. Conclusions: We provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease. Competing Interests: Potential conflicts of interest. A. G. R. reports receiving reagents to her institution from Illumina Inc for work outside of this project. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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