Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38730242.
- Also identified by DOI 10.1038/s41467-024-48287-0 and PMC identifier 11087577.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Ubiquitin-Protein Ligases
- Encephalitis, Herpes Simplex
- Mutation
- Herpesvirus 1, Human