Abstract
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.
Highlights
Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic fatal viral encephalitis in Western countries with a mortality rate of ~70% in the absence of antiviral treatment [1]
We report here 2 cases of adult HSE in patients with very rare variants in mannan-binding lectin serine protease 2 (MASP-2), the gene encoding a protease considered as the central activator of the lectin pathway of the complement system, because of its ability to form complexes with several pattern recognition molecules including mannose-binding lectin (MBL), collectins (CL-L1 and CL-K1) and ficolins (FCN1, FCN2 and FCN3 called M, L- and H-ficolin respectively)
MASP-2 is involved in the complement system as the central protein of the lectin pathway, which is triggered by specific recognition of pathogens
Summary
Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic fatal viral encephalitis in Western countries with a mortality rate of ~70% in the absence of antiviral treatment [1]. It occurs in 2–4 individuals per million and per year, with a bimodal age distribution including children, mainly as a result of primary infection [2, 3], and adults over the age of 50 years, as a result of reactivation from a latent infection [4]. Two studies in adult patients identified variants in genes not directly involved in the TLR3/IFN pathway, indicating that other genes/pathways may be associated with the development of HSE [17, 18]
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