Herpes simplex encephalitis in adult patients with MASP-2 deficiency

Stéphanie Bibert, Jocelyne Piret, Mathieu Quinodoz, Emilie Collinet, Vincent Zoete, Olivier Michielin, Rafik Menasria, Pascal Meylan, Titus Bihl, Véronique Erard, Florence Fellmann, Carlo Rivolta (+3 others)
2019 PLoS Pathogens  
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)
more » ... r 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.
doi:10.1371/journal.ppat.1008168 pmid:31869396 pmcid:PMC6944389 fatcat:cmopixzfenbifcqzqjlk277owi