Herpes simplex encephalitis in adult patients with MASP-2 deficiency.
Stéphanie BibertJocelyne PiretMathieu QuinodozEmilie CollinetVincent ZoeteOlivier MichielinRafik MenasriaPascal MeylanTitus BihlVéronique ErardFlorence FellmannCarlo RivoltaGuy BoivinPierre-Yves BochudPublished in: PLoS pathogens (2019)
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.
Keyphrases
- herpes simplex virus
- copy number
- signaling pathway
- end stage renal disease
- binding protein
- chronic kidney disease
- toll like receptor
- immune response
- inflammatory response
- early onset
- replacement therapy
- prognostic factors
- epithelial mesenchymal transition
- gene expression
- type diabetes
- machine learning
- dna binding
- white matter
- high glucose
- electronic health record
- cell proliferation
- drug induced
- metabolic syndrome
- endothelial cells
- brain injury
- low density lipoprotein
- induced apoptosis
- data analysis
- high fat diet induced
- blood brain barrier
- insulin resistance