Herpes simplex encephalitis in adult patients with MASP-2 deficiency

Résumé fourni par la source

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. Author summaryHuman herpes virus type 1 (HSV-1) infects a large number of individuals during their life, with manifestations usually limited to mild and self-limiting inflammation of the oral mucosa (cold sore).However, HSV-1 can cause a very severe disease of the brain called Herpes simplex encephalitis (HSE) in 1 out of 250'000-500'000 individuals per year.The reasons why HSV-1 can cause such a devastating disease in a very limited number of individuals are unknown.Increasing evidence suggests that susceptibility to HSE in children can results from genetic variations in the immune system, in particular in a viral detection

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