title: Mendelian predisposition to herpes simplex encephalitis.
abstract: Herpes simplex encephalitis (HSE) is the most common sporadic viral encephalitis in the Western world. The pathogenesis of HSE, which affects a small minority of HSV-1-infected individuals, has long remained elusive. Mendelian defects in the TLR3-interferon (IFN) and IFN-responsive pathways were recently shown to predispose to HSE, at least in some children. Autosomal recessive STAT-1 deficiency and X-linked NEMO deficiency were found in children with both mycobacterial disease and HSE. Autosomal recessive UNC-93B deficiency and autosomal dominant TLR3 deficiency were then described in children with isolated HSE. These discoveries provided proof-of-principle that HSE may result from a novel group of single-gene inborn errors of interferon (IFN)-mediated immunity. The TLR3-UNC-93B-dependent production of IFN-α/β and IFN-λ is essential to confer protective immunity to HSV-1 in the central nervous system during the course of primary infection in childhood.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Paris, France; Université Paris René Descartes, Necker Medical School, Paris, France.
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D020803:Encephalitis, Herpes Simplex / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018259:Herpesvirus 1, Human; D006801:Humans; D007223:Infant; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D050794:STAT1 Transcription Factor / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C454130:UNC93B1 protein, human