{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:15:57Z","timestamp":1772997357458,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Interferons (IFNs) are critical for immune defense against pathogens. While type\u2010I and \u2010III IFNs have been reported to inhibit SARS\u2010CoV\u20102 replication, the antiviral effect and mechanism of type\u2010II IFN against SARS\u2010CoV\u20102 remain largely unknown. Here, we evaluate the antiviral activity of type\u2010II IFN (IFN\u03b3) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFN\u03b3 suppresses SARS\u2010CoV\u20102 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFN\u03b3 treatment does not significantly modulate the expression of SARS\u2010CoV\u20102 entry\u2010related factors and induces a similar level of pro\u2010inflammatory response in human lung tissues when compared with IFN\u03b2 treatment. Mechanistically, we show that overexpression of indoleamine 2,3\u2010dioxygenase 1 (IDO1), which is most profoundly induced by IFN\u03b3, substantially restricts the replication of ancestral SARS\u2010CoV\u20102 and the Alpha and Delta variants. Meanwhile, loss\u2010of\u2010function study reveals that IDO1 knockdown restores SARS\u2010CoV\u20102 replication restricted by IFN\u03b3 in Calu3 cells. We further found that the treatment of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010tryptophan, a substrate of IDO1, partially rescues\u00a0the IFN\u03b3\u2010mediated inhibitory effect on SARS\u2010CoV\u20102 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type\u2010II IFN potently inhibits SARS\u2010CoV\u20102 replication through IDO1\u2010mediated antiviral response.\n                  <\/jats:p>","DOI":"10.1002\/jmv.29472","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T14:04:37Z","timestamp":1708351477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Type\u2010II IFN inhibits SARS\u2010CoV\u20102 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3\u2010dioxygenase\u2010mediated pathways"],"prefix":"10.1002","volume":"96","author":[{"given":"Dong","family":"Yang","sequence":"first","affiliation":[{"name":"Xianghu Laboratory Hangzhou Zhejiang China"},{"name":"State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine The 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