Herpes simplex virus encephalitis in human UNC-93B deficiency.
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.
Casrouge
Armanda
A
Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes, INSERM, U550, Faculté de Médecine Necker, Paris 75015, France.
Zhang
Shen-Ying
SY
Eidenschenk
Céline
C
Jouanguy
Emmanuelle
E
Puel
Anne
A
Yang
Kun
K
Alcais
Alexandre
A
Picard
Capucine
C
Mahfoufi
Nora
N
Nicolas
Nathalie
N
Lorenzo
Lazaro
L
Plancoulaine
Sabine
S
Sénéchal
Brigitte
B
Geissmann
Frédéric
F
Tabeta
Koichi
K
Hoebe
Kasper
K
Du
Xin
X
Miller
Richard L
RL
Héron
Bénédicte
B
Mignot
Cyril
C
de Villemeur
Thierry Billette
TB
Lebon
Pierre
P
Dulac
Olivier
O
Rozenberg
Flore
F
Beutler
Bruce
B
Tardieu
Marc
M
Abel
Laurent
L
Casanova
Jean-Laurent
JL
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
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