[Genetic susceptibility to herpes simplex encephalitis]

Abstract

Herpes simplex encephalitis (HSE) is a rare but severe complication of frequent and mostly benign infection with herpes simplex virus (HSV). Although rapid and sensitive diagnosis tools and active antiviral drugs are available, HSE morbidity/mortality levels remain unsatisfactory. Molecular and cellular determinants of HSE are incompletely understood. The rarity and severity of the disease have suggested an increased susceptibility of some subjects to HSV infection. Numerous experimental studies have investigated the respective role of host and viral factors in HSE. The results of these studies have illustrated the major role of the innate immune response, in particular interferons (IFNs), in limiting access of the virus into and/or virus replication in the central nervous system (CNS). In a few children with HSE, specific defects of the immune innate response have been identified, which impair the IFN-α/β and IFN-λ production of fibroblasts and/or neurons infected with HSV and render these cells more permissive to infection. The mutations affect proteins involved in the IFN pathway induced by stimulation of the TLR3 receptor. The patients' susceptibility to infection is restricted to HSV CNS invasion, underlining the major role of TLR3 in CNS protection against viral infection. The incomplete clinical penetrance of these molecular defects suggests that other factors (age, infectious dose) are involved in HSE. Whether pathogenesis of adult HSE is similar has not been investigated.