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Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase

Author

Listed:
  • Stéphanie Bibert

    (University Hospital and University of Lausanne)

  • Mathieu Quinodoz

    (Institute of Molecular and Clinical Ophthalmology Basel (IOB)
    University of Basel
    University of Leicester)

  • Sylvain Perriot

    (University Hospital and University of Lausanne)

  • Fanny S. Krebs

    (University of Lausanne
    Ludwig Institute for Cancer Research)

  • Maxime Jan

    (University of Lausanne)

  • Rita C. Malta

    (University Hospital and University of Lausanne)

  • Emilie Collinet

    (University Hospital and University of Lausanne)

  • Mathieu Canales

    (University Hospital and University of Lausanne)

  • Amandine Mathias

    (University Hospital and University of Lausanne)

  • Nicole Faignart

    (University Hospital and University of Lausanne)

  • Eliane Roulet-Perez

    (University Hospital and University of Lausanne)

  • Pascal Meylan

    (University Hospital and University of Lausanne)

  • René Brouillet

    (University Hospital and University of Lausanne)

  • Onya Opota

    (University Hospital and University of Lausanne)

  • Leyder Lozano-Calderon

    (University Hospital and University of Lausanne)

  • Florence Fellmann

    (University of Lausanne)

  • Nicolas Guex

    (University of Lausanne)

  • Vincent Zoete

    (University of Lausanne
    Ludwig Institute for Cancer Research
    SIB Swiss Institute of Bioinformatics)

  • Sandra Asner

    (University Hospital and University of Lausanne
    University Hospital and University of Lausanne)

  • Carlo Rivolta

    (Institute of Molecular and Clinical Ophthalmology Basel (IOB)
    University of Basel
    University of Leicester)

  • Renaud Pasquier

    (University Hospital and University of Lausanne
    University Hospital and University of Lausanne)

  • Pierre-Yves Bochud

    (University Hospital and University of Lausanne)

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_007014.4:c.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.

Suggested Citation

  • Stéphanie Bibert & Mathieu Quinodoz & Sylvain Perriot & Fanny S. Krebs & Maxime Jan & Rita C. Malta & Emilie Collinet & Mathieu Canales & Amandine Mathias & Nicole Faignart & Eliane Roulet-Perez & Pas, 2024. "Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48287-0
    DOI: 10.1038/s41467-024-48287-0
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