Herpes simplex encephalitis in adult patients with MASP-2 deficiency

Autoři: Stéphanie Bibert aff001;  Jocelyne Piret aff002;  Mathieu Quinodoz aff003;  Emilie Collinet aff001;  Vincent Zoete aff004;  Olivier Michielin aff004;  Rafik Menasria aff002;  Pascal Meylan aff001;  Titus Bihl aff008;  Véronique Erard aff008;  Florence Fellmann aff009;  Carlo Rivolta aff003;  Guy Boivin aff002;  Pierre-Yves Bochud aff001
Působiště autorů: Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland aff001;  Research center in Infectious Diseases, CHU of Quebec and Laval University, Quebec city, Canada aff002;  Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne Switzerland aff003;  Ludwig Institute for Cancer research, University of Lausanne, Lausanne, Switzerland aff004;  Molecular Modeling Group, Swiss Institute of Bioinformatics, Quartier Sorge, Génopode, Lausanne, Switzerland aff005;  Department of Oncology, University Hospital and University of Lausanne, Lausanne, Switzerland aff006;  Institute of Microbiology, Department of Laboratory Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland aff007;  Canton Hospital of Fribourg, Fribourg, Switzerland aff008;  Department of Genetics, Laboratoire National de Santé, Dudelange, Luxembourg aff009;  Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom aff010
Vyšlo v časopise: Herpes simplex encephalitis in adult patients with MASP-2 deficiency. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008168
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008168


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.

Klíčová slova:

Alleles – Complement system – Cytokines – Chemokines – Molecular dynamics – Mouse models – Sequence motif analysis – Lectins


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Hygiena a epidemiologie Infekční lékařství Laboratoř

Článek vyšel v časopise

PLOS Pathogens

2019 Číslo 12
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