Herpes simplex virus 2 encephalitis in a patient heterozygous for a TLR3 mutation.

Susceptibility to herpes simplex virus type 1 (HSV-1) encephalitis (HSE-1) in otherwise healthy individuals, in the course of primary infection, can be caused by single-gene inborn errors of Toll-like receptor 3 (TLR3) dependent, interferon (IFN)-α/β-mediated immunity,1,2 or by single-gene inborn errors of snoRNA31.3 These variations underlie infections of the forebrain, whereas mutations of DBR1 underlie infections of the brainstem.3 HSV-2 encephalitis (HSE-2) is typically observed in neonates, albeit also rarely in older children and adults.4 Its manifestations include altered level of consciousness, cranial neuropathies or more extensive brainstem encephalitis, hemiparesis, hemisensory loss, and permanent neurologic deficit.4 MRI in HSE-2 may show normal findings, nonspecific white matter, orbitofrontal, mesial temporal lobe, or brainstem lesions. Inborn errors of immunity underlying HSE-2 have not been described.