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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-2-28
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pubmed:abstractText |
The receptors for interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma activate components of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, leading to the formation of at least two transcription factor complexes. STAT1 interacts with STAT2 and p48/IRF-9 to form the transcription factor IFN-stimulated gene factor 3 (ISGF3). STAT1 dimers form gamma-activated factor (GAF). ISGF3 is induced mainly by IFN-alpha/beta, and GAF by IFN-gamma, although both factors can be activated by both types of IFN. Individuals with mutations in either chain of the IFN-gamma receptor (IFN-gammaR) are susceptible to infection with mycobacteria. A heterozygous STAT1 mutation that impairs GAF but not ISGF3 activation has been found in other individuals with mycobacterial disease. No individuals with deleterious mutations in the IFN-alpha/beta signaling pathway have been described. We report here two unrelated infants homozygous with respect to mutated STAT1 alleles. Neither IFN-alpha/beta nor IFN-gamma activated STAT1-containing transcription factors. Like individuals with IFN-gammaR deficiency, both infants suffered from mycobacterial disease, but unlike individuals with IFN-gammaR deficiency, both died of viral disease. Viral multiplication was not inhibited by recombinant IFN-alpha/beta in cell lines from the two individuals. Inherited impairment of the STAT1-dependent response to human IFN-alpha/beta thus results in susceptibility to viral disease.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:Al GhonaiumAbdulazizA,
pubmed-author:Al-GazlanSuleimanS,
pubmed-author:Al-HajjarSamiS,
pubmed-author:Al-JumaahSulimanS,
pubmed-author:Al-MohsenIbrahim ZaidIZ,
pubmed-author:Al-RayesHassanH,
pubmed-author:CasanovaJean-LaurentJL,
pubmed-author:ChapgierArianeA,
pubmed-author:DupuisStéphanieS,
pubmed-author:EidPierreP,
pubmed-author:EidenschenkCélineC,
pubmed-author:FieschiClaireC,
pubmed-author:FrayhaHusnH,
pubmed-author:GresserIonI,
pubmed-author:JouanguyEmmanuelleE,
pubmed-author:SchreiberRobert DRD,
pubmed-author:TufenkejiHaysamH,
pubmed-author:YangKunK
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pubmed:issnType |
Print
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
388-91
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12590259-Amino Acid Substitution,
pubmed-meshheading:12590259-Antiviral Agents,
pubmed-meshheading:12590259-Base Sequence,
pubmed-meshheading:12590259-Consanguinity,
pubmed-meshheading:12590259-DNA,
pubmed-meshheading:12590259-DNA-Binding Proteins,
pubmed-meshheading:12590259-Female,
pubmed-meshheading:12590259-Humans,
pubmed-meshheading:12590259-Infant,
pubmed-meshheading:12590259-Interferon Type I,
pubmed-meshheading:12590259-Interferon-gamma,
pubmed-meshheading:12590259-Male,
pubmed-meshheading:12590259-Mycobacterium Infections,
pubmed-meshheading:12590259-Pedigree,
pubmed-meshheading:12590259-Recombinant Proteins,
pubmed-meshheading:12590259-STAT1 Transcription Factor,
pubmed-meshheading:12590259-Sequence Deletion,
pubmed-meshheading:12590259-Signal Transduction,
pubmed-meshheading:12590259-Trans-Activators,
pubmed-meshheading:12590259-Virus Diseases
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pubmed:year |
2003
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pubmed:articleTitle |
Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency.
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pubmed:affiliation |
Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-INSERM UMR550, Faculté de Médecine Necker-Enfants Malades, 75015 Paris, France.
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pubmed:publicationType |
Journal Article,
In Vitro,
Case Reports,
Research Support, Non-U.S. Gov't
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