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

Child Humans Male Adolescent Female Influenza, Human / genetics DEAD Box Protein 58 / genetics Receptors, Immunologic / genetics Polymorphism, Single Nucleotide Interferons / genetics Communicable Diseases
DDX58 RIG-I receptor host genetics pediatric influenza susceptibility

Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
28 11 2022
Historique:
received: 06 04 2022
accepted: 18 08 2022
pubmed: 21 8 2022
medline: 1 12 2022
entrez: 20 8 2022
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1093/infdis/jiac350 PMID: 35986912 PMC: PMC10205622
pubmed: 35986912
pii: 6672861
doi: 10.1093/infdis/jiac350
pmc: PMC10205622
doi:

Substances chimiques

DEAD Box Protein 58 EC 3.6.4.13
Receptors, Immunologic 0
Interferons 9008-11-1
RIGI protein, human EC 3.6.1.-

Types de publication

Journal Article Research Support, N.I.H., Intramural Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2030-2036

Subventions

Organisme : NHGRI NIH HHS
ID : U01 HG008685
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI084011
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI084011
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117626
Pays : United States
Organisme : NIH HHS
ID : AI154470
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI154470
Pays : United States

Informations de copyright

© 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.

Déclaration de conflit d'intérêts

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.

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Auteurs

Sanghun 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.
ORCID: 0000-0002-0573-9555

Yu 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.

Margaret Newhams (M)

Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.

Tanya 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.

Paul G Thomas (PG)

Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.

Peter M 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.

Mark W Hall (MW)

Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.

Laura L Loftis (LL)

Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA.

Natalie Z Cvijanovich (NZ)

Division of Critical Care Medicine, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.

Keiko M Tarquinio (KM)

Division of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.

Adam J Schwarz (AJ)

Department of Pediatrics, Children's Hospital of Orange County, Orange, California, USA.

Scott L Weiss (SL)

Division of Critical Care, Department of Anesthesiology and Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Neal J Thomas (NJ)

Department of Pediatrics, Penn State Hershey Children's Hospital, Penn State University College of Medicine, Hershey, Pennsylvania, USA.

Barry Markovitz (B)

Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, California, USA.

Melissa L Cullimore (ML)

Division of Pediatric Critical Care, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Ronald C Sanders (RC)

Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock, Arkansas, USA.

Matt S 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.

Janice E Sullivan (JE)

Division of Pediatric Critical Care, University of Louisville School of Medicine and Norton Children's Hospital, Louisville, Kentucky, USA.

Natasha B Halasa (NB)

Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Melania M Bembea (MM)

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

John S Giuliano (JS)

Division of Critical Care, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.

Katri V Typpo (KV)

Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, Arizona, USA.

Ryan A Nofziger (RA)

Division of Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio, USA.

Steven L Shein (SL)

Division of Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.

Michele Kong (M)

Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Bria M 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.

Scott T Weiss (ST)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Christoph 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.

Helen C 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.

Adrienne G 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.
ORCID: 0000-0002-3084-3071

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Grippe humaine › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › RNA nucleotidyltransferases › RNA helicases › DEAD-box RNA helicases › Protéine-58 à domaine DEAD › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › DDX58 Is Associated With Susceptibility to...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladies transmissibles › DDX58 Is Associated With Susceptibility to...