| Title: |
Herpes simplex encephalitis in adult patients with MASP-2 deficiency |
| Authors: |
Bibert, Stéphanie; Piret, Jocelyne; Quinodoz, Mathieu; Collinet, Emilie; Zoete, Vincent; Michielin, Olivier; Menasria, Rafik; Meylan, Pascal; Bihl, Titus; Erard, Véronique; Fellmann, Florence; Rivolta, Carlo; Boivin, Guy; Bochud, Pierre-Yves |
| Source: |
ISSN: 1553-7366 ; PLOS pathogens, vol. 15, no. 12 (2019) e1008168. |
| Publication Year: |
2019 |
| Collection: |
Université de Genève: Archive ouverte UNIGE |
| Subject Terms: |
Adult; Animals; Encephalitis; Herpes Simplex / genetics; Herpes Simplex / immunology; Herpes Simplex / metabolism; Humans; Immunity; Innate / genetics; Lectins / genetics; Lectins / metabolism; Male; Mannose-Binding Lectin / metabolism; Mannose-Binding Protein-Associated Serine Proteases / deficiency; Mannose-Binding Protein-Associated Serine Proteases / genetics; Mannose-Binding Protein-Associated Serine Proteases / immunology; Mice; Inbred C57BL; Transgenic |
| Description: |
We report here two cases of Herpes simplex virus encephalitis (HSE) in adult patients with very rare, previously uncharacterized, non synonymous heterozygous G634R and R203W substitution in mannan-binding lectin serine protease 2 (MASP2), a gene encoding a key protease of the lectin pathway of the complement system. None of the 2 patients had variants in genes involved in the TLR3-interferon signaling pathway. Both MASP2 variants induced functional defects in vitro, including a reduced (R203W) or abolished (G634R) protein secretion, a lost capability to cleave MASP-2 precursor into its active form (G634R) and an in vivo reduced antiviral activity (G634R). In a murine model of HSE, animals deficient in mannose binding lectins (MBL, the main pattern recognition molecule associated with MASP-2) had a decreased survival rate and an increased brain burden of HSV-1 compared to WT C57BL/6J mice. Altogether, these data suggest that MASP-2 deficiency can increase susceptibility to adult HSE. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/31869396; unige:190583 |
| Availability: |
https://archive-ouverte.unige.ch/unige:190583 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.902B5EB1 |
| Database: |
BASE |