{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:36:26Z","timestamp":1792632986849,"version":"4.5.0"},"reference-count":63,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC core funding of the MRC Human Immunology Unit"],"award-info":[{"award-number":["MRC core funding of the MRC Human Immunology Unit"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12014\/8"],"award-info":[{"award-number":["MC_UU_12014\/8"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N017552\/1"],"award-info":[{"award-number":["MR\/N017552\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["100954"],"award-info":[{"award-number":["100954"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["H2020 MSCA-ITN GA 675278 EDGE"],"award-info":[{"award-number":["H2020 MSCA-ITN GA 675278 EDGE"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The Zika virus (ZIKV) has received much attention due to an alarming increase in cases of neurological disorders including congenital Zika syndrome associated with infection. To date, there is no effective treatment available. An immediate response by the innate immune system is crucial for effective control of the virus. Using CRISPR\/Cas9-mediated knockouts in A549 cells, we investigated the individual contributions of the RIG-I-like receptors MDA5 and RIG-I to ZIKV sensing and control of this virus by using a Brazilian ZIKV strain. We show that RIG-I is the main sensor for ZIKV in A549 cells. Surprisingly, we observed that loss of RIG-I and consecutive type I interferon (IFN) production led to virus-induced apoptosis. ZIKV non-structural protein NS5 was reported to interfere with type I IFN receptor signaling. Additionally, we show that ZIKV NS5 inhibits type I IFN induction. Overall, our study highlights the importance of RIG-I-dependent ZIKV sensing for the prevention of virus-induced cell death and shows that NS5 inhibits the production of type I IFN.<\/jats:p>","DOI":"10.3390\/cells9061476","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:00:56Z","timestamp":1592478056000},"page":"1476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death"],"prefix":"10.3390","volume":"9","author":[{"given":"Mirjam","family":"Schilling","sequence":"first","affiliation":[{"name":"Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bridgeman","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicki","family":"Gray","sequence":"additional","affiliation":[{"name":"MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7089-982X","authenticated-orcid":false,"given":"Jonny","family":"Hertzog","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-3247","authenticated-orcid":false,"given":"Philip","family":"Hublitz","sequence":"additional","affiliation":[{"name":"Genome Engineering Facility, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Kohl","sequence":"additional","affiliation":[{"name":"MRC-Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-835X","authenticated-orcid":false,"given":"Jan","family":"Rehwinkel","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1126\/science.aaf5036","article-title":"Zika virus in the Americas: Early epidemiological and genetic findings","volume":"352","author":"Faria","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41579-018-0134-9","article-title":"The evolution of Zika virus from Asia to the Americas","volume":"17","author":"Liu","year":"2019","journal-title":"Nat. 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