Herpes simplex virus type 1 (HSV1) is frequent but usually benign in childhood Between 40% and 60% of adolescents have circulating anti-HSV1
antibodies by the age of 16 years. However, HSV1
infection is occasionally associated with
encephalitis (
fever, seizures, frequently altered consciousness, elevated CSF
protein levels and lymphocyte counts, and EEG and MRI abnormalities). The etiologic diagnosis is based on lumbar puncture and detection of the viral genome or specific
antibodies in CSF. Despite
antiviral treatment with
acyclovir, there is a high risk of sequelae such as
epilepsy and severe
mental retardation. The response to microbial pathogens is largely influenced by the host's genetic background (factors of resistance and predisposition), including Mendelian monogenic determinants. During the period 1985-2004, we conducted a molecular study based on a candidate gene strategy in 85 children with HSV1
encephalitis. The children belonging to 51 families, of which 7 were consanguineous. Five different mutations have so far been identified in 8 of these families, affecting genes encoding either
Toll-like receptor 3 (TLR3) or a
protein involved in intracellular signal transduction from this receptor to the
interferon "a gene promoter", preventing the synthesis of this key molecule in the anti-HSV1 immune response.