IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro.
IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro.
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DOI：
10.1038/s41467-021-24817-y
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发表时间：
2021-07-28
影响因子：
16.6
通讯作者：
Kirchhoff F
中科院分区：
文献类型：
--
作者：
Prelli Bozzo C;Nchioua R;Volcic M;Koepke L;Krüger J;Schütz D;Heller S;Stürzel CM;Kmiec D;Conzelmann C;Müller J;Zech F;Braun E;Groß R;Wettstein L;Weil T;Weiß J;Diofano F;Rodríguez Alfonso AA;Wiese S;Sauter D;Münch J;Goffinet C;Catanese A;Schön M;Boeckers TM;Stenger S;Sato K;Just S;Kleger A;Sparrer KMJ;Kirchhoff F
干扰素诱导的跨膜蛋白（IFITM 1、2和3）可以限制病毒病原体，但已报道了对冠状病毒的促病毒和抗病毒活性。在这里，我们表明，人工过表达IFITMs阻断SARS-CoV-2感染。然而，内源性IFITM表达支持SARS-CoV-2在人肺细胞中的有效感染。我们的研究结果表明，SARS-CoV-2刺突蛋白与IFITMs相互作用，并劫持它们进行有效的病毒感染。IFITM蛋白在人肺、肠、心脏和脑细胞中表达并进一步被干扰素诱导。IFITM衍生肽和靶向抗体抑制SARS-CoV-2进入人肺细胞、心肌细胞和肠道类器官并复制。我们的研究结果表明，IFITM蛋白是辅助因子的有效SARS-CoV-2感染的人类细胞类型代表在体内的目标病毒的传播，传播和发病机制，是潜在的治疗方法的目标。IFITM蛋白可以抑制几种病毒，但对SARS-CoV-2感染的影响尚不清楚。在这里，作者表明，内源性IFITMs支持SARS-CoV-2感染在不同的体外模型结合刺突和增强病毒进入。
Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) can restrict viral pathogens, but pro- and anti-viral activities have been reported for coronaviruses. Here, we show that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. However, endogenous IFITM expression supports efficient infection of SARS-CoV-2 in human lung cells. Our results indicate that the SARS-CoV-2 Spike protein interacts with IFITMs and hijacks them for efficient viral infection. IFITM proteins were expressed and further induced by interferons in human lung, gut, heart and brain cells. IFITM-derived peptides and targeting antibodies inhibit SARS-CoV-2 entry and replication in human lung cells, cardiomyocytes and gut organoids. Our results show that IFITM proteins are cofactors for efficient SARS-CoV-2 infection of human cell types representing in vivo targets for viral transmission, dissemination and pathogenesis and are potential targets for therapeutic approaches. IFITM proteins can inhibit several viruses, but effects on SARS-CoV-2 infection are not well understood. Here, the authors show that endogenous IFITMs support SARS-CoV-2 infection in different in vitro models by binding spike and enhancing virus entry.
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