학술논문
Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase
Document Type
article
Author
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; Pascal Meylan; René Brouillet; Onya Opota; Leyder Lozano-Calderon; Florence Fellmann; Nicolas Guex; Vincent Zoete; Sandra Asner; Carlo Rivolta; Renaud Du Pasquier; Pierre-Yves Bochud
Source
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024)
Subject
Language
English
ISSN
2041-1723
Abstract
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.