Inhibition of SARS-CoV-2 by type I and type III interferons.
Inhibition of SARS-CoV-2 by type I and type III interferons.
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DOI：
10.1074/jbc.ac120.013788
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发表时间：
2020-10-09
期刊：
影响因子：
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通讯作者：
Weber F
中科院分区：
文献类型：
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作者：
Felgenhauer U;Schoen A;Gad HH;Hartmann R;Schaubmar AR;Failing K;Drosten C;Weber F
最近出现的严重急性呼吸道综合征冠状病毒-2（SARS-CoV-2）是毁灭性的COVID-19肺病大流行的病原体。在这里，我们测试了I型抗病毒干扰素（IFN-α）和III型抗病毒干扰素（IFN-λ）对SARS-CoV-2的抑制活性，并将其与2003年出现的抗SARS-CoV-1的抑制活性进行了比较。使用两种哺乳动物上皮细胞系（人Calu-3和猿Vero E6），我们发现这两种IFN剂量依赖性地抑制SARS-CoV-2。相反，SARS-CoV-1在这些细胞系中仅受IFN-α的限制。SARS-CoV-2通常表现出比SARS-CoV-1更广泛的IFN敏感性。此外，ruxolitinib，一种IFN触发的Janus激酶/信号转导和转录信号激活剂的抑制剂，促进了SARS-CoV-2在IFN感受态Calu-3细胞中的复制。我们的结论是，SARS-CoV-2是敏感的外源性干扰素。这一发现表明，I型，尤其是不良反应倾向较小的III型IFN是管理COVID-19的良好候选药物。
The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2) is the causative agent of the devastating COVID-19 lung disease pandemic. Here, we tested the inhibitory activities of the antiviral interferons of type I (IFN-α) and type III (IFN-λ) against SARS–CoV-2 and compared them with those against SARS–CoV-1, which emerged in 2003. Using two mammalian epithelial cell lines (human Calu-3 and simian Vero E6), we found that both IFNs dose-dependently inhibit SARS–CoV-2. In contrast, SARS–CoV-1 was restricted only by IFN-α in these cell lines. SARS–CoV-2 generally exhibited a broader IFN sensitivity than SARS–CoV-1. Moreover, ruxolitinib, an inhibitor of IFN-triggered Janus kinase/signal transducer and activator of transcription signaling, boosted SARS–CoV-2 replication in the IFN-competent Calu-3 cells. We conclude that SARS–CoV-2 is sensitive to exogenously added IFNs. This finding suggests that type I and especially the less adverse effect–prone type III IFN are good candidates for the management of COVID-19.