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.
Publication types
-
Case Reports
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Child, Preschool
-
Cytokines / biosynthesis
-
Encephalitis, Herpes Simplex / genetics*
-
Encephalitis, Herpes Simplex / immunology
-
Female
-
Genetic Predisposition to Disease*
-
Herpesvirus 1, Human* / immunology
-
Humans
-
Infant
-
Interferon-alpha / biosynthesis
-
Interferon-alpha / immunology
-
Interferon-beta / biosynthesis
-
Interferon-beta / immunology
-
Interferon-gamma / biosynthesis
-
Interferon-gamma / immunology
-
Interferons / biosynthesis*
-
Interferons / immunology
-
Leukocytes, Mononuclear / immunology
-
Male
-
Membrane Transport Proteins / deficiency*
-
Membrane Transport Proteins / genetics
-
Membrane Transport Proteins / physiology*
-
Mutation
-
Pedigree
-
Signal Transduction
-
Toll-Like Receptor 3 / agonists
-
Toll-Like Receptor 3 / physiology
-
Toll-Like Receptors / agonists
-
Toll-Like Receptors / physiology
Substances
-
Cytokines
-
Interferon-alpha
-
Membrane Transport Proteins
-
TLR3 protein, human
-
Toll-Like Receptor 3
-
Toll-Like Receptors
-
UNC93B1 protein, human
-
Interferon-beta
-
Interferon-gamma
-
Interferons