1 Ocak 2023 Dergi makalesi Açık Erişim

Tepe, Zeynep Gunes; Yazici, Yilmaz Yucehan; Tank, Umut; Kose, Ladin Isik; Ozer, Murat; Aytekin, Caner; Belkaya, Serkan

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{
  "@context": "https://schema.org/", 
  "@id": 261179, 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "affiliation": "Ihsan Dogramaci Bilkent Univ, Fac Sci, Dept Mol Biol & Genet, Ankara, Turkey", 
      "name": "Tepe, Zeynep Gunes"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Ihsan Dogramaci Bilkent Univ, Fac Sci, Dept Mol Biol & Genet, Ankara, Turkey", 
      "name": "Yazici, Yilmaz Yucehan"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Ihsan Dogramaci Bilkent Univ, Fac Sci, Dept Mol Biol & Genet, Ankara, Turkey", 
      "name": "Tank, Umut"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Ihsan Dogramaci Bilkent Univ, Fac Sci, Dept Mol Biol & Genet, Ankara, Turkey", 
      "name": "Kose, Ladin Isik"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Dr Sami Ulus Matern & Childrens Hlth & Dis Traini, Dept Pediat Immunol, Ankara, Turkey", 
      "name": "Ozer, Murat"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Dr Sami Ulus Matern & Childrens Hlth & Dis Traini, Dept Pediat Immunol, Ankara, Turkey", 
      "name": "Aytekin, Caner"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Ihsan Dogramaci Bilkent Univ, Fac Sci, Dept Mol Biol & Genet, Ankara, Turkey", 
      "name": "Belkaya, Serkan"
    }
  ], 
  "datePublished": "2023-01-01", 
  "description": "Human herpesvirus-6 (HHV-6) infection can rarely cause life-threatening conditions, such as encephalitis, in otherwise healthy children, with unclear pathogenesis. We studied a child who presented with acute HHV-6 encephalitis at the age of 10 months and who was homozygous for a novel missense mutation in IRAK4, encoding interleukin-1 receptor-associated kinase 4, identified by whole-exome sequencing. We tested the damaging impact of this mutation in silico by molecular dynamics simulations and in vitro by biochemical and functional experiments utilizing cell lines and patient's cells. We found that the mutation is severely hypomorphic, impairing both the expression and function of IRAK-4. Patient's leukocytes had barely detectable levels of IRAK-4 and diminished anti-viral immune responses to various stimuli inducing different Toll-like receptors and cytosolic nucleic acid sensors. Overall, these findings suggest that acute HHV-6 encephalitis can result from inborn errors of immunity to virus. This study represents the first report of isolated acute HHV-6 infection causing encephalitis in an inherited primary immunodeficiency, notably autosomal recessive (AR) partial IRAK-4 deficiency, and the first report of AR IRAK-4 deficiency presenting with a severe viral disease, notably HHV-6 encephalitis upon an acute infection, thereby expanding the clinical spectrum of IRAK-4 deficiency.", 
  "headline": "Inherited IRAK-4 Deficiency in Acute Human Herpesvirus-6 Encephalitis", 
  "identifier": 261179, 
  "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", 
  "license": "http://www.opendefinition.org/licenses/cc-by", 
  "name": "Inherited IRAK-4 Deficiency in Acute Human Herpesvirus-6 Encephalitis", 
  "url": "https://aperta.ulakbim.gov.tr/record/261179"
}