{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T09:04:43Z","timestamp":1793783083304,"version":"4.6.1"},"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"israel science foundation","award":["3814\/19"],"award-info":[{"award-number":["3814\/19"]}]},{"name":"Ben B. and Joyce E. Eisenberg Foundation"},{"name":"jack ma foundation"},{"DOI":"10.13039\/501100004752","name":"state government of victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"national health and medical research council","doi-asserted-by":"publisher","award":["1160838"],"award-info":[{"award-number":["1160838"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"national health and medical research council","doi-asserted-by":"publisher","award":["1125704"],"award-info":[{"award-number":["1125704"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Type I Interferons (IFN-Is) are a family of cytokines which play a major role in inhibiting viral infection. Resultantly, many viruses have evolved mechanisms in which to evade the IFN-I response. Here we tested the impact of expression of 27 different SARS-CoV-2 genes in relation to their effect on IFN production and activity using three independent experimental methods. We identified six gene products; NSP6, ORF6, ORF7b, NSP1, NSP5 and NSP15, which strongly (&gt;10-fold) blocked MAVS-induced (but not TRIF-induced) IFN\u03b2 production. Expression of the first three of these SARS-CoV-2 genes specifically blocked MAVS-induced IFN\u03b2-promoter activity, whereas all six genes induced a collapse in IFN\u03b2 mRNA levels, corresponding with suppressed IFN\u03b2 protein secretion. Five of these six genes furthermore suppressed MAVS-induced activation of IFN\u03bbs, however with no effect on IFN\u03b1 or IFN\u03b3 production. In sharp contrast, SARS-CoV-2 infected cells remained extremely sensitive to anti-viral activity exerted by added IFN-Is. None of the SARS-CoV-2 genes were able to block IFN-I signaling, as demonstrated by robust activation of Interferon Stimulated Genes (ISGs) by added interferon. This, despite the reduced levels of STAT1 and phospho-STAT1, was likely caused by broad translation inhibition mediated by NSP1. Finally, we found that a truncated ORF7b variant that has arisen from a mutant SARS-CoV-2 strain harboring a 382-nucleotide deletion associating with mild disease (\u0394382 strain identified in Singapore &amp; Taiwan in 2020) lost its ability to suppress type I and type III IFN production. In summary, our findings support a multi-gene process in which SARS-CoV-2 blocks IFN-production, with ORF7b as a major player, presumably facilitating evasion of host detection during early infection. However, SARS-CoV-2 fails to suppress IFN-I signaling thus providing an opportunity to exploit IFN-Is as potential therapeutic antiviral drugs.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009800","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T13:43:17Z","timestamp":1629985397000},"page":"e1009800","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":130,"title":["SARS-CoV-2 suppresses IFN\u03b2 production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon"],"prefix":"10.1371","volume":"17","author":[{"given":"Maya","family":"Shemesh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9725-4220","authenticated-orcid":true,"given":"Turgut E.","family":"Aktepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Deerain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2493-3465","authenticated-orcid":true,"given":"Julie L.","family":"McAuley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle D.","family":"Audsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra T.","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-1726","authenticated-orcid":true,"given":"Damian F. J.","family":"Purcell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5391-5659","authenticated-orcid":true,"given":"Victoria","family":"Urin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-066X","authenticated-orcid":true,"given":"Rune","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-3906","authenticated-orcid":true,"given":"Gregory W.","family":"Moseley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6613-8350","authenticated-orcid":true,"given":"Jason M.","family":"Mackenzie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-4157","authenticated-orcid":true,"given":"Daniel","family":"Harari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ppat.1009800.ref001","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1098\/rspb.1957.0048","article-title":"Virus interference. 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