{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:31:14Z","timestamp":1789885874598,"version":"4.0.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI146352"],"award-info":[{"award-number":["AI146352"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["EY032149"],"award-info":[{"award-number":["EY032149"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>ORAI1 and stromal interaction molecule 1 (STIM1) are the critical mediators of store-operated Ca2+ entry by acting as the pore subunit and an endoplasmic reticulum\u2013resident signaling molecule, respectively. In addition to Ca2+ signaling, STIM1 is also involved in regulation of the type I IFN (IFN-I) response. To examine their potential role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated ORAI1 and STIM1 knockout human HEK293\u2013angiotensin-converting enzyme 2 cells and checked their responses. STIM1 knockout cells showed strong resistance to SARS-CoV-2 infection as a result of enhanced IFN-I response. On the contrary, ORAI1 deletion induced high susceptibility to SARS-CoV-2 infection. Mechanistically, ORAI1 knockout cells showed reduced homeostatic cytoplasmic Ca2+ concentration and severe impairment in tonic IFN-I signaling. Transcriptome analysis showed downregulation of multiple antiviral signaling pathways in ORAI1 knockout cells, likely because of reduced expression of the Ca2+-dependent transcription factors of the AP-1 family and MEF2C. Accordingly, modulation of homeostatic Ca2+ concentration by pretreatment with ORAI1 blocker or agonist could influence baseline IFNB expression and resistance to SARS-CoV-2 infection in a human lung epithelial cell line. Our results identify a novel role of ORAI1-mediated Ca2+ signaling in regulating the tonic IFN-I levels, which determine host resistance to SARS-CoV-2 infection.<\/jats:p>","DOI":"10.4049\/jimmunol.2100742","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T17:20:17Z","timestamp":1637774417000},"page":"74-84","source":"Crossref","is-referenced-by-count":27,"title":["ORAI1 Limits SARS-CoV-2 Infection by Regulating Tonic Type I IFN Signaling"],"prefix":"10.1093","volume":"208","author":[{"given":"Beibei","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-6141","authenticated-orcid":false,"given":"Arunachalam","family":"Ramaiah","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of California , Irvine, Irvine, CA"},{"name":"Tata Institute for Genetics and Society, Center at inStem , Bangalore, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Gustavo","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Hasiakos","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA"},{"name":"Division of Oral Biology and Medicine, UCLA School of Dentistry , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaithilingaraja","family":"Arumugaswami","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California , Los Angeles, Los Angeles, CA"},{"name":"California NanoSystems Institute, University of California , Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-095X","authenticated-orcid":false,"given":"Sonal","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"2025021008471119700_r1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.chom.2016.01.006","article-title":"The evolution of antiviral defense systems","volume":"19","author":"tenOever","year":"2016","journal-title":"Cell Host Microbe"},{"key":"2025021008471119700_r2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/ni.3123","article-title":"Control of adaptive immunity by the innate immune system","volume":"16","author":"Iwasaki","year":"2015","journal-title":"Nat. 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