TLR3 mutations in adult patients with herpes simplex virus and varicella-zoster virus encephalitis

Abstract

Defects in genes of the Toll-like receptor 3 (TLR3) pathway are associated with susceptibility to herpes simplex virus type 1 encephalitis (HSE). We analyzed a cohort of 11 adult Italian patients in whom viral encephalitis developed. We detected 2 rare missense mutations in TLR3: 1 in a patient with HSE (p.Leu297Val) and 1 in a patient with varicella-zoster virus encephalitis (p.Leu199Phe). Both mutations are extremely rare in human populations and have pathogenicity scores highly suggestive of a functional effect. Data herein expand the phenotypic spectrum of TLR3 mutations to varicella-zoster virus encephalitis and support the role of TLR3 genetic defects as risk factors for HSE in adults.