{"doi":"10.1172/jci139980","title":"Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency","abstract":"causing life-threatening herpes simplex encephalitis (HSE) of the forebrain or brainstem, respectively (3). HSE is the most common sporadic viral encephalitis affecting otherwise healthy humans, at least in Western countries. Its incidence peaks between the ages of 3 months and 6 years, earlier than would be predicted from age at primary infection alone (1). During HSE, the infection is restricted to the CNS, with the forebrain affected in about 95% of cases and the brainstem affected in the remaining approximately 5% of cases (1, 4). There are usually no mucocutaneous lesions, no detectable viremia, and no lesions of internal organs other than the brain. The advent of acyclovir treatment has decreased the mortality of HSE from about 75% to about 20% (5). However, 40%-60% of survivors suffer mild-to-severe (10%-20%) neurological sequelae (6-8). With the exception of the identification of the causal virus, the pathogenesis of HSE remained unexplained until 2006-2007, Inborn errors of TLR3-dependent IFN-/-and IFN--mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-/ and IFN- 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-2b or IFN-, 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-2b or IFN-. 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-/ are essential for anti-HSV-1 immunity in the CNS.","journal":"Journal of Clinical Investigation","year":2020,"id":53517,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":116,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104148,"name":"Jérémy Manry","orcid":"0000-0001-5998-2051","position":1,"is_corresponding":false},{"id":104462,"name":"Jie Chen","orcid":"0000-0002-5354-4170","position":2,"is_corresponding":false},{"id":104146,"name":"Jérémie Rosain","orcid":"0000-0002-2822-161X","position":3,"is_corresponding":false},{"id":104164,"name":"Yoann Seeleuthner","orcid":"0000-0002-1878-8567","position":4,"is_corresponding":false},{"id":276122,"name":"Omar AbuZaitun","orcid":null,"position":5,"is_corresponding":false},{"id":104152,"name":"Lazaro Lorenzo","orcid":"0000-0001-6648-8684","position":6,"is_corresponding":false},{"id":104489,"name":"Taushif Khan","orcid":"0000-0002-7917-8965","position":7,"is_corresponding":false},{"id":273546,"name":"Mary L. Hasek","orcid":"0000-0001-8902-6431","position":8,"is_corresponding":false},{"id":276123,"name":"Nicholas Hernandez","orcid":null,"position":9,"is_corresponding":false},{"id":104163,"name":"Benedetta Bigio","orcid":"0000-0001-7291-5638","position":10,"is_corresponding":false},{"id":104484,"name":"Peng Zhang","orcid":"0000-0002-6129-567X","position":11,"is_corresponding":false},{"id":273547,"name":"Romain Lévy","orcid":"0000-0002-6393-0198","position":12,"is_corresponding":false},{"id":273548,"name":"Shai Shrot","orcid":"0000-0001-8954-3244","position":13,"is_corresponding":false},{"id":273549,"name":"Eduardo J. Garcia Reino","orcid":"0000-0002-4781-3864","position":14,"is_corresponding":false},{"id":273550,"name":"Yoon Seung Lee","orcid":"0000-0002-9988-8905","position":15,"is_corresponding":false},{"id":273551,"name":"Soraya Boucherit","orcid":"0000-0002-8819-7594","position":16,"is_corresponding":false},{"id":273552,"name":"Mélodie Aubart","orcid":"0000-0002-4383-7930","position":17,"is_corresponding":false},{"id":273553,"name":"Rik Gijsbers","orcid":"0000-0003-0191-3904","position":18,"is_corresponding":false},{"id":104147,"name":"Vivien Béziat","orcid":"0000-0002-4020-824X","position":19,"is_corresponding":false},{"id":273554,"name":"Zhi Li","orcid":"0000-0003-4422-4914","position":20,"is_corresponding":false},{"id":273555,"name":"Sandra Pellegrini","orcid":"0000-0001-5837-7589","position":21,"is_corresponding":false},{"id":263171,"name":"Flore Rozenberg","orcid":"0000-0001-7212-2021","position":22,"is_corresponding":false},{"id":263173,"name":"Nico Marr","orcid":"0000-0002-1927-7072","position":23,"is_corresponding":false},{"id":241316,"name":"Isabelle Meyts","orcid":"0000-0003-1214-0302","position":24,"is_corresponding":false},{"id":241303,"name":"Bertrand Boisson","orcid":"0000-0001-5240-3555","position":25,"is_corresponding":false},{"id":57371,"name":"Aurélie Cobat","orcid":"0000-0001-7209-6257","position":26,"is_corresponding":false},{"id":241304,"name":"Jacinta Bustamante","orcid":"0000-0002-3439-2482","position":27,"is_corresponding":false},{"id":104140,"name":"Qian Zhang","orcid":"0000-0002-9040-3289","position":28,"is_corresponding":false},{"id":276124,"name":"Emmanuelle Jouangy","orcid":null,"position":29,"is_corresponding":false},{"id":241301,"name":"Laurent Abel","orcid":"0000-0001-7016-6493","position":30,"is_corresponding":false},{"id":258739,"name":"Raz Somech","orcid":"0000-0001-6648-9425","position":31,"is_corresponding":false},{"id":57373,"name":"Jean-Laurent Casanova","orcid":"0000-0002-7782-4169","position":32,"is_corresponding":false},{"id":57374,"name":"Shen-Ying Zhang","orcid":"0000-0002-9449-3672","position":33,"is_corresponding":false},{"id":104138,"name":"Paul Bastard","orcid":"0000-0002-5926-8437","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-18T20:45:25.145885Z","pmid":"32960813","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}