[Genetic predisposition to herpetic meningo-encephalitis in children]

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.