{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:54:28Z","timestamp":1792234468780,"version":"4.4.0"},"reference-count":54,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"77","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,11,25]]},"abstract":"<jats:p>\n                    Herpes simplex virus 1 (HSV-1) infects several billion people worldwide and can cause life-threatening herpes simplex encephalitis (HSE) in some patients. Monogenic defects in components of the type I interferon system have been identified in patients with HSE, emphasizing the role of inborn errors of immunity underlying HSE pathogenesis. Here, we identify compound heterozygous loss-of-function mutations in the gene\n                    <jats:italic>GTF3A<\/jats:italic>\n                    encoding for transcription factor IIIA (TFIIIA), a component of the RNA polymerase III complex, in a patient with common variable immunodeficiency and HSE. Patient fibroblasts and\n                    <jats:italic>GTF3A<\/jats:italic>\n                    gene\u2013edited cells displayed impaired HSV-1\u2013induced innate immune responses and enhanced HSV-1 replication. Chromatin immunoprecipitation sequencing analysis identified the 5\n                    <jats:italic>S<\/jats:italic>\n                    ribosomal RNA pseudogene 141 (\n                    <jats:italic>RNA5SP141<\/jats:italic>\n                    ), an endogenous ligand of the RNA sensor RIG-I, as a transcriptional target of TFIIIA.\n                    <jats:italic>GTF3A<\/jats:italic>\n                    mutant cells exhibited diminished\n                    <jats:italic>RNA5SP141<\/jats:italic>\n                    expression and abrogated RIG-I activation upon HSV-1 infection. Our work unveils a crucial role for TFIIIA in transcriptional regulation of a cellular RIG-I agonist and shows that\n                    <jats:italic>GTF3A<\/jats:italic>\n                    genetic defects lead to impaired cell-intrinsic anti\u2013HSV-1 responses and can predispose to HSE.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.abq4531","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T13:58:32Z","timestamp":1668779912000},"source":"Crossref","is-referenced-by-count":43,"title":["<i>GTF3A<\/i>\n                    mutations predispose to herpes simplex encephalitis by disrupting biogenesis of the host-derived RIG-I ligand\n                    <i>RNA5SP141<\/i>"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1715-0665","authenticated-orcid":true,"given":"Leslie","family":"Naesens","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium."},{"name":"Primary Immunodeficiency Research Lab, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium."},{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port St.\u00a0Lucie, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santoshi","family":"Muppala","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port St.\u00a0Lucie, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1929-3870","authenticated-orcid":true,"given":"Dhiraj","family":"Acharya","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port St.\u00a0Lucie, FL, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, IL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-8924","authenticated-orcid":true,"given":"Josephine","family":"Nemegeer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium."},{"name":"Laboratory of Molecular Signaling and Cell death, VIB-UGent Center for Inflammation Research, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-5461","authenticated-orcid":true,"given":"Delfien","family":"Bogaert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium."},{"name":"Primary Immunodeficiency Research Lab, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-0027","authenticated-orcid":true,"given":"Jung-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port St.\u00a0Lucie, FL, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, IL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Staes","sequence":"additional","affiliation":[{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6525-9422","authenticated-orcid":true,"given":"Veronique","family":"Debacker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium."},{"name":"Primary Immunodeficiency Research Lab, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-8770","authenticated-orcid":true,"given":"Pieter","family":"De Bleser","sequence":"additional","affiliation":[{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium."},{"name":"Laboratory of Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6636-5537","authenticated-orcid":true,"given":"Marieke","family":"De Bruyne","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine, Ghent University, Ghent, Belgium."},{"name":"Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5609-6895","authenticated-orcid":true,"given":"Elfride","family":"De Baere","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine, Ghent University, Ghent, Belgium."},{"name":"Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-5360","authenticated-orcid":true,"given":"Michiel","family":"van Gent","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port St.\u00a0Lucie, FL, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, IL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2520-7625","authenticated-orcid":true,"given":"GuanQun","family":"Liu","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port St.\u00a0Lucie, FL, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, IL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4376-6834","authenticated-orcid":true,"given":"Bart N.","family":"Lambrecht","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium."},{"name":"Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-3357","authenticated-orcid":true,"given":"Jens","family":"Staal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium."},{"name":"Laboratory of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2114-2844","authenticated-orcid":true,"given":"Tessa","family":"Kerre","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium."},{"name":"Department of Hematology, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-582X","authenticated-orcid":true,"given":"Rudi","family":"Beyaert","sequence":"additional","affiliation":[{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium."},{"name":"Laboratory of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1476-0583","authenticated-orcid":true,"given":"Jonathan","family":"Maelfait","sequence":"additional","affiliation":[{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium."},{"name":"Laboratory of Molecular Signaling and Cell death, VIB-UGent Center for Inflammation Research, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-5655","authenticated-orcid":true,"given":"Simon J.","family":"Tavernier","sequence":"additional","affiliation":[{"name":"Primary Immunodeficiency Research Lab, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium."},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium."},{"name":"Department of Biomolecular Medicine, Ghent University, Ghent, Belgium."},{"name":"Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium."},{"name":"Laboratory of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2163-2598","authenticated-orcid":true,"given":"Michaela U.","family":"Gack","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port St.\u00a0Lucie, FL, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, IL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9161-7361","authenticated-orcid":true,"given":"Filomeen","family":"Haerynck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium."},{"name":"Primary Immunodeficiency Research Lab, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.19.237149"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.spid.2004.09.007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2937"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.017"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091313-103409"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139522"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.2129insight4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0288-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01085-19"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1779"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.015"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-017-0005-y"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.019"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0672-3"},{"key":"e_1_3_3_16_2","first-page":"1","article-title":"Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee","author":"Tangye S. G.","year":"2022","unstructured":"S. G.\u00a0Tangye, W.\u00a0Al-Herz, A.\u00a0Bousfiha, C.\u00a0Cunningham-Rundles, J. L.\u00a0Franco, S. M.\u00a0Holland, C.\u00a0Klein, T.\u00a0Morio, E.\u00a0Oksenhendler, C.\u00a0Picard, A.\u00a0Puel, J.\u00a0Puck, M.\u00a0R.\u00a0J.\u00a0Sepp\u00e4nen, R.\u00a0Somech, H. C.\u00a0Su, K. E.\u00a0Sullivan, T. R.\u00a0Torgerson, I.\u00a0Meyts,Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee. J. Clin. Immunol. ,1\u201335 (2022).","journal-title":"J. Clin. Immunol."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000999"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1801"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(80)80048-1"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(89)90345-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb03825.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7MT00256D"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2019.110955"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.74"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/hdy.2013.63"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(92)90897-S"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02464-y"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0172-x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5947"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05732"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg161"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3661"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00737-3"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01209-5"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140520"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00430-1"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.031"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104599"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2019.0015"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109500"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2948"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.08.011"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05286"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-018-0027-y"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2009947117"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000929"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.08.014"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abn3800"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1061"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20169-8"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-00884-1"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07106"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.abq4531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T07:51:07Z","timestamp":1705391467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.abq4531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,25]]},"references-count":54,"journal-issue":{"issue":"77","published-print":{"date-parts":[[2022,11,25]]}},"alternative-id":["10.1126\/sciimmunol.abq4531"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.abq4531","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742416217.793597910","asserted-by":"object"}]},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,25]]},"article-number":"eabq4531"}}