Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency

The Journal of Experimental Medicine
Nicholas HernandezJean-Laurent Casanova

Abstract

Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.

References

Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·X Y FuJ E Darnell
Oct 1, 1988·Molecular and Cellular Biology·P StaeheliO Haller
Mar 13, 2001·Annual Review of Immunology·T TaniguchiN Tanaka
May 5, 2001·Genome Research·P C Ng, S Henikoff
Mar 30, 2005·The Journal of Experimental Medicine·Carine Asselin-PaturelGiorgio Trinchieri
Aug 29, 2006·PLoS Genetics·Ariane ChapgierJean-Laurent Casanova
Dec 8, 2006·Journal of Virology·Iris KoernerPeter Staeheli
Sep 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pamela I OsterlundIlkka Julkunen
Sep 18, 2007·Science·Shen-Ying ZhangJean-Laurent Casanova
Nov 28, 2007·Annual Review of Pathology·Jeffery K Taubenberger, David M Morens
Sep 2, 2008·American Journal of Human Genetics·Ruth McQuillanJames F Wilson
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Nov 6, 2009·The New England Journal of Medicine·Erik-Oliver GlockerChristoph Klein
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Joanna JaworskaLouis Flamand
May 7, 2010·The New England Journal of Medicine·Edgar BautistaKarl G Nicholson
May 29, 2010·The American Journal of Pathology·Wun-Ju ShiehSherif R Zaki
Sep 15, 2010·Molecular Biology and Evolution·Nina Stoletzki, Adam Eyre-Walker
Oct 27, 2010·The Journal of Experimental Medicine·Henning LauterbachHubertus Hochrein
Apr 15, 2011·Genes and Immunity·S NingG N Barber
Apr 27, 2011·The American Journal of Gastroenterology·Bernadette BegueFrank M Ruemmele
Jun 8, 2011·Pediatrics·Fatimah S DawoodUNKNOWN Emerging Infections Program Network
Jan 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lauren A O'DonnellGlenn F Rall
Apr 24, 2012·Immunity·George R Stark, James E Darnell
Jun 2, 2012·Current Opinion in Immunology·Stephanie Boisson-DupuisJean-Laurent Casanova
Sep 22, 2012·The Journal of Clinical Investigation·Kirby D JohnsonEmery H Bresnick
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Dec 4, 2012·Nucleic Acids Research·Irina RusinovaPaul J Hertzog
Feb 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sophie HambletonRichard E Randall
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yuval ItanJean-Laurent Casanova

❮ Previous
Next ❯

Citations

Dec 12, 2018·Current Opinion in Pediatrics·Joshua D Doyle, Angela P Campbell
Jun 7, 2019·Medical Microbiology and Immunology·Michelle M ThomsenTrine H Mogensen
Jun 21, 2019·The Journal of Experimental Medicine·Hye Kyung LimShen-Ying Zhang
Aug 30, 2019·Current Opinion in Pediatrics·Huie Jing, Helen C Su
Sep 6, 2019·Proceedings of the National Academy of Sciences of the United States of America·Scott B DrutmanJean-Laurent Casanova
Dec 7, 2019·Human Genetics·Amalio Telenti, Julia di Iulio
Jan 30, 2020·The New England Journal of Medicine·Scott B DrutmanJean-Laurent Casanova
Feb 25, 2020·The Journal of Experimental Medicine·Conor GruberDusan Bogunovic
May 30, 2020·Mucosal Immunology·Alain Fischer
Sep 7, 2019·Critical Care : the Official Journal of the Critical Care Forum·Sara Clohisey, John Kenneth Baillie
Jul 5, 2019·The Journal of Experimental Medicine·Nicholas HernandezXavier Bossuyt
Jun 20, 2019·The Journal of Experimental Medicine·Serkan BelkayaJean-Laurent Casanova
Oct 24, 2018·Frontiers in Cellular and Infection Microbiology·Kirsty R ShortCarolien E van de Sandt
Apr 21, 2020·F1000Research·Gregory M Constantine, Michail S Lionakis
Jul 7, 2020·Frontiers in Immunology·Sophie JungAurélien Guffroy
Sep 26, 2020·Science·Qian ZhangJean-Laurent Casanova
Nov 7, 2019·Current Opinion in Pediatrics·Huie Jing, Helen C Su
Apr 15, 2020·Human Genetics·Emmanuelle Jouanguy
Jul 23, 2020·Frontiers in Immunology·Madalina Elena Carter-TimofteTrine H Mogensen
Feb 7, 2020·Human Genetics·Qian Zhang
Sep 18, 2020·Oncoimmunology·Cléa MelenotteLaurence Zitvogel
Aug 21, 2020·The Journal of Experimental Medicine·Nicole PalacioPablo Penaloza-MacMaster
Jan 5, 2021·The Journal of Clinical Investigation·Daxing GaoShen-Ying Zhang
Sep 23, 2020·The Journal of Clinical Investigation·Paul BastardShen-Ying Zhang
Dec 2, 2020·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Arnaud J WautletChristopher D Codispoti
Apr 15, 2020·Annual Review of Pathology·Jean-Laurent Casanova, Laurent Abel
Feb 6, 2021·The Journal of Experimental Medicine·Paul BastardJean-Laurent Casanova
Nov 14, 2020·Mucosal Immunology·Jessica L Forbester, Ian R Humphreys
Dec 6, 2020·Nature Reviews. Genetics·Andrew J KwokJulian C Knight
Nov 11, 2020·Journal of Clinical Medicine·Jasna Omersel, Nataša Karas Kuželički
Nov 25, 2020·JCI Insight·Michael S AbersLuigi D Notarangelo
Dec 1, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Florian GotheChristopher J A Duncan
Mar 25, 2021·Trends in Microbiology·Silke Stertz, Benjamin G Hale
Apr 4, 2021·Viruses·Joe McKellarCaroline Goujon
Mar 18, 2021·European Journal of Immunology·Isabelle Meyts, Jean-Laurent Casanova
Nov 7, 2019·Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie·B LormeauE Jeziorski
Feb 4, 2021·Annual Review of Immunology·Erica G Schmitt, Megan A Cooper

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
biopsies
PCR
fluorescence-activated cell sorting
electrophoresis
Assay
immunoprecipitation
Illumina sequencing
RNA-seq

Software Mentioned

Genome Analysis Toolkit
GATK
STAR
GeneMANIA
R
Prism
HTseq
FastQC
GnomAD
SAMtools

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The New England Journal of Medicine
Caroline B Hall
American Journal of Respiratory and Critical Care Medicine
Marianna Sockrider, Julie Katkin
© 2022 Meta ULC. All rights reserved