Herpes simplex virus encephalitis of childhood: inborn errors of central nervous system cell-intrinsic immunity

• Published in: Human genetics Vol. 139; no. 6-7; pp. 911 - 918
• Main Author: Zhang, Shen-Ying
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2020; Springer; Springer Nature B.V
• Subjects: Antiviral agents; Biomedical and Life Sciences; Biomedicine; Brain stem; Central nervous system; Central Nervous System Diseases - epidemiology; Central Nervous System Diseases - genetics; Central Nervous System Diseases - immunology; Central Nervous System Diseases - virology; Child; Children; Encephalitis; Encephalitis, Herpes Simplex - epidemiology; Encephalitis, Herpes Simplex - genetics; Encephalitis, Herpes Simplex - immunology; Encephalitis, Herpes Simplex - virology; Forebrain; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Herpes simplex; Herpes Simplex - complications; Herpes Simplex - immunology; Herpes Simplex - virology; Herpes simplex virus; Herpes viruses; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - pathogenicity; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Human Genetics; Human genetics of infectious diseases; Humans; Immunity; Immunity, Cellular - immunology; Immunology; Metabolic Diseases; Molecular Medicine; Mutation; Nervous system; Review; TLR3 protein; Toll-like receptors; Virus diseases; α-Interferon
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-020-02127-5

Herpes simplex virus 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Over the last 15 years, human genetic and immunological studies have provided proof-of-principle that childhood HSE can result from inborn errors of central nervous system (CNS)-specific, cell-intrinsic immunity to HSV-1. HSE-causing mutations of eight genes disrupt known (TLR3-dependent IFN-α/β immunity) and novel (dependent on DBR1 or snoRNA31) antiviral mechanisms. Monogenic inborn errors confer susceptibility to forebrain (TLR3-IFN or snoRNA31) or brainstem (DBR1) HSE. Most of these disorders display incomplete clinical penetrance, with the possible exception of DBR1 deficiency. They account for a small, but non-negligible proportion of cases (about 7%). These findings pave the way for the gradual definition of the genetic and immunological architecture of childhood HSE, with both biological and clinical implications.