Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase.
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Herpesvirus Humano 1
/
Encefalitis por Herpes Simple
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Ubiquitina-Proteína Ligasas
/
Mutación
Límite:
Female
/
Humans
/
Infant
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza