Herpes Simplex Virus Encephalitis in Human UNC-93B Deficiency

TLDR

Herpes simplex virus‑1 encephalitis is the most common sporadic viral encephalitis in the West, yet its pathogenesis remains unclear and it occurs in only a minority of otherwise healthy HSV‑1‑infected individuals, suggesting that monogenic immune defects may underlie severe infections. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in UNC‑93B, leading to impaired interferon‑α/β and -λ antiviral responses. HSE can result from a single‑gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies.

Abstract

Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-alpha/beta and -lambda antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity.