title: Herpes simplex virus encephalitis in human UNC-93B deficiency.
abstract: Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-alpha/beta and -lambda antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity.
authors.affiliation: Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes, INSERM, U550, Faculté de Médecine Necker, Paris 75015, France.
authors.forename: Armanda
authors.initials: A
authors.lastname: Casrouge
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Céline
authors.initials: C
authors.lastname: Eidenschenk
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jouanguy
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alcais
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Nora
authors.initials: N
authors.lastname: Mahfoufi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicolas
authors.forename: Lazaro
authors.initials: L
authors.lastname: Lorenzo
authors.forename: Sabine
authors.initials: S
authors.lastname: Plancoulaine
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sénéchal
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
authors.forename: Koichi
authors.initials: K
authors.lastname: Tabeta
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Richard L
authors.initials: RL
authors.lastname: Miller
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Héron
authors.forename: Cyril
authors.initials: C
authors.lastname: Mignot
authors.forename: Thierry Billette
authors.initials: TB
authors.lastname: de Villemeur
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Flore
authors.initials: F
authors.lastname: Rozenberg
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D020803:Encephalitis, Herpes Simplex / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007223:Infant; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007372:Interferons / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D010375:Pedigree; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000502:physiology; D051193:Toll-Like Receptors / Q000819:agonists / Q000502:physiology
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D026901:Membrane Transport Proteins; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; C454130:UNC93B1 protein, human; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons