Herpes simplex virus encephalitis of childhood: inborn errors of central nervous system cell-intrinsic immunity.
Shen-Ying ZhangPublished in: Human genetics (2020)
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.
Keyphrases
- herpes simplex virus
- immune response
- genome wide
- single cell
- patient safety
- inflammatory response
- cell therapy
- toll like receptor
- early life
- endothelial cells
- childhood cancer
- sars cov
- cerebrospinal fluid
- copy number
- stem cells
- gene expression
- blood brain barrier
- dna methylation
- south africa
- mesenchymal stem cells
- induced pluripotent stem cells
- drug induced
- replacement therapy