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Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase.
Bibert, Stéphanie; Quinodoz, Mathieu; Perriot, Sylvain; Krebs, Fanny S; Jan, Maxime; Malta, Rita C; Collinet, Emilie; Canales, Mathieu; Mathias, Amandine; Faignart, Nicole; Roulet-Perez, Eliane; Meylan, Pascal; Brouillet, René; Opota, Onya; Lozano-Calderon, Leyder; Fellmann, Florence; Guex, Nicolas; Zoete, Vincent; Asner, Sandra; Rivolta, Carlo; Du Pasquier, Renaud; Bochud, Pierre-Yves.
Afiliación
  • Bibert S; Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Quinodoz M; Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
  • Perriot S; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • Krebs FS; Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
  • Jan M; Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Malta RC; Department of Oncology UNIL-CHUV, Computer-Aided Molecular Engineering, University of Lausanne, Lausanne, Switzerland.
  • Collinet E; Ludwig Institute for Cancer Research, Lausanne, Switzerland.
  • Canales M; Bioinformatics Competence Center, University of Lausanne, Lausanne, Switzerland.
  • Mathias A; Pediatric Infectious Diseases and Vaccinology Unit, Woman-Mother-Child Department, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Faignart N; Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Roulet-Perez E; Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Meylan P; Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Brouillet R; Department of Pediatrics, Child Neurology Unit, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Opota O; Department of Pediatrics, Child Neurology Unit, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Lozano-Calderon L; Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Fellmann F; Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Guex N; Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Zoete V; Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Asner S; The ColLaboratory, University of Lausanne, Lausanne, Switzerland.
  • Rivolta C; Bioinformatics Competence Center, University of Lausanne, Lausanne, Switzerland.
  • Du Pasquier R; Department of Oncology UNIL-CHUV, Computer-Aided Molecular Engineering, University of Lausanne, Lausanne, Switzerland.
  • Bochud PY; Ludwig Institute for Cancer Research, Lausanne, Switzerland.
Nat Commun ; 15(1): 3969, 2024 May 10.
Article en En | MEDLINE | ID: mdl-38730242
ABSTRACT
Encephalitis is a rare and potentially fatal manifestation of herpes simplex type 1 infection. Following genome-wide genetic analyses, we identified a previously uncharacterized and very rare heterozygous variant in the E3 ubiquitin ligase WWP2, in a 14-month-old girl with herpes simplex encephalitis. The p.R841H variant (NM_007014.4c.2522G > A) impaired TLR3 mediated signaling in inducible pluripotent stem cells-derived neural precursor cells and neurons; cells bearing this mutation were also more susceptible to HSV-1 infection compared to control cells. The p.R841H variant increased TRIF ubiquitination in vitro. Antiviral immunity was rescued following the correction of p.R841H by CRISPR-Cas9 technology. Moreover, the introduction of p.R841H in wild type cells reduced such immunity, suggesting that this mutation is linked to the observed phenotypes.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Herpesvirus Humano 1 / Encefalitis por Herpes Simple / Ubiquitina-Proteína Ligasas / Mutación Límite: Female / Humans / Infant Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Herpesvirus Humano 1 / Encefalitis por Herpes Simple / Ubiquitina-Proteína Ligasas / Mutación Límite: Female / Humans / Infant Idioma: En Año: 2024 Tipo del documento: Article