{"doi":"10.1084/jem.20231725","title":"SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency","abstract":"Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.","journal":"The Journal of Experimental Medicine","year":2024,"id":430211,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1203398,"name":"Vanja Lundberg","orcid":null,"position":1,"is_corresponding":false},{"id":104161,"name":"Jérémie Le Pen","orcid":"0000-0001-7025-9526","position":2,"is_corresponding":false},{"id":1168978,"name":"Jiayi Yuan","orcid":"0000-0001-8315-7609","position":3,"is_corresponding":false},{"id":57367,"name":"Danyel Lee","orcid":"0000-0003-3124-0245","position":4,"is_corresponding":false},{"id":1233198,"name":"Francesca Pinci","orcid":"0000-0002-5013-9663","position":5,"is_corresponding":false},{"id":309131,"name":"Stefano Volpi","orcid":"0000-0002-7129-868X","position":6,"is_corresponding":false},{"id":57370,"name":"Koji Nakajima","orcid":"0000-0002-3548-5330","position":7,"is_corresponding":false},{"id":336954,"name":"Vincent Bondet","orcid":"0000-0002-6534-0984","position":8,"is_corresponding":false},{"id":1233647,"name":"Sanna Åkesson","orcid":null,"position":9,"is_corresponding":false},{"id":305209,"name":"Noopur V. 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