Herpes simplex encephalitis in adult patients with MASP-2 deficiency.

Adult Animals Encephalitis, Herpes Simplex / genetics Humans Immunity, Innate / genetics Lectins / genetics Male Mannose-Binding Lectin / metabolism Mannose-Binding Protein-Associated Serine Proteases / deficiency Mice, Inbred C57BL Mice, Transgenic

Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
12 2019
Historique:
received: 11 06 2019
accepted: 29 10 2019
revised: 06 01 2020
pubmed: 24 12 2019
medline: 7 3 2020
entrez: 24 12 2019
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1371/journal.ppat.1008168 PMID: 31869396 PMC: PMC6944389
pubmed: 31869396
doi: 10.1371/journal.ppat.1008168
pii: PPATHOGENS-D-19-01033
pmc: PMC6944389
doi:

Substances chimiques

Lectins 0
Mannose-Binding Lectin 0
MASP-2 protein, mouse EC 3.4.21.-
MASP2 protein, human EC 3.4.21.-
Mannose-Binding Protein-Associated Serine Proteases EC 3.4.21.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008168

Subventions

Organisme : CIHR
ID : 148361
Pays : Canada

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Stéphanie Bibert (S)

Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
ORCID: 0000-0001-5170-7506

Jocelyne Piret (J)

Research center in Infectious Diseases, CHU of Quebec and Laval University, Quebec city, Canada.

Mathieu Quinodoz (M)

Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne Switzerland.
ORCID: 0000-0002-9841-4433

Emilie Collinet (E)

Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.

Vincent Zoete (V)

Ludwig Institute for Cancer research, University of Lausanne, Lausanne, Switzerland.
Molecular Modeling Group, Swiss Institute of Bioinformatics, Quartier Sorge, Génopode, Lausanne, Switzerland.

Olivier Michielin (O)

Ludwig Institute for Cancer research, University of Lausanne, Lausanne, Switzerland.
Molecular Modeling Group, Swiss Institute of Bioinformatics, Quartier Sorge, Génopode, Lausanne, Switzerland.
Department of Oncology, University Hospital and University of Lausanne, Lausanne, Switzerland.

Rafik Menasria (R)

Research center in Infectious Diseases, CHU of Quebec and Laval University, Quebec city, Canada.

Pascal Meylan (P)

Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
Institute of Microbiology, Department of Laboratory Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.

Titus Bihl (T)

Canton Hospital of Fribourg, Fribourg, Switzerland.
ORCID: 0000-0001-6374-3520

Véronique Erard (V)

Canton Hospital of Fribourg, Fribourg, Switzerland.

Florence Fellmann (F)

Department of Genetics, Laboratoire National de Santé, Dudelange, Luxembourg.

Carlo Rivolta (C)

Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne Switzerland.
Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.

Guy Boivin (G)

Research center in Infectious Diseases, CHU of Quebec and Laval University, Quebec city, Canada.

Pierre-Yves Bochud (PY)

Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-2208-4757

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Eucaryotes › Animaux › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Maladies du système nerveux › Encéphalite › Encéphalite infectieuse › Encéphalite virale › Encéphalite à herpès simplex › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Lectines › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Lectines › Lectines liant le mannose › Lectine liant le mannose › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Immunoprotéines › Protéines du système du complément › Enzymes activatrices du complément › Complement C3-C5 Convertases › Mannose-Binding Protein-Associated Serine Proteases › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Herpes simplex encephalitis in adult patients...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Herpes simplex encephalitis in adult patients...