ArticleThe Journal of clinical investigation2021
Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 109 citations in OpenAlex.
- Host Genetic Susceptibility and Antiviral Immunity Shape the Pathogenesis and Outcomes of Herpes Simplex Encephalitis.Biology · 2026Review
- Two novel kindreds with autosomal recessive STAT2 deficiency.Journal of human immunity · 2026Article
- iPSC-based macrophage models reveal interferon-dependent control of RSV permissiveness and syncytia formation.Microbiology spectrum · 2026Article
- Guideline for the Diagnosis and Management of Heritable IFNAR1 Deficiency in Oceania.Journal of paediatrics and child health · 2026Review
- Genetic mechanisms underlying host susceptibility to central nervous system viral infections.Current opinion in infectious diseases · 2026Review
- Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis.The Journal of experimental medicine · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- Recurrent severe viral infection in a child with inherited complete TBK1 deficiency.Journal of human immunity · 2026Article
- Genetic and autoimmune predispositions to fulminant viral hepatitis in children.Frontiers in immunology · 2026Review
- The cell-mediated adaptive immune response to herpes simplex virus type 1 encephalitis: mechanisms and clinical implications.Frontiers in immunology · 2026Review
- The seven enigmas of SARS-CoV-2: from the past to the future.Journal of human immunity · 2025Article
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages.Journal of clinical immunology · 2025Article
- Review
- Herpesvirus-associated diseases: biomarkers and advancements in clinical research.Virology journal · 2025Review
- Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus CNS infection.Journal of neuroinflammation · 2025Article
- Decoding Immunobiology Through Genetic Errors of Immunity.Annual review of immunology · 2025Review
- A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.The Journal of experimental medicine · 2025Article
- Human genetic and immunological determinants of SARS-CoV-2 infection and multisystem inflammatory syndrome in children.Clinical and experimental immunology · 2025Review
- Human DBR1 deficiency impairs stress granule-dependent PKR antiviral immunity.The Journal of experimental medicine · 2025Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors at 9 institutions in 6 countries.
Funding
Abstract
Inborn errors of TLR3-dependent IFN-α/β- and IFN-λ-mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-α/β and IFN-λ are unknown. We report a child homozygous for a genomic deletion of the entire coding sequence and part of the 3'-UTR of the last exon of IFNAR1, who died of HSE at the age of 2 years. An older cousin died following vaccination against measles, mumps, and rubella at 12 months of age, and another 17-year-old cousin homozygous for the same variant has had other, less severe, viral illnesses. The encoded IFNAR1 protein is expressed on the cell surface but is truncated and cannot interact with the tyrosine kinase TYK2. The patient's fibroblasts and EBV-B cells did not respond to IFN-α2b or IFN-β, in terms of STAT1, STAT2, and STAT3 phosphorylation or the genome-wide induction of IFN-stimulated genes. The patient's fibroblasts were susceptible to viruses, including HSV-1, even in the presence of exogenous IFN-α2b or IFN-β. HSE is therefore a consequence of inherited complete IFNAR1 deficiency. This viral disease occurred in natural conditions, unlike those previously reported in other patients with IFNAR1 or IFNAR2 deficiency. This experiment of nature indicates that IFN-α/β are essential for anti-HSV-1 immunity in the CNS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.