Type I interferons (IFNs) are a first line of defence against viral infections. Upon infection, a first small wave of early type I IFN, mainly IFN-β and particularly IFN-α4, are induced and bind to the type I IFN receptor (IFNAR) to amplify the IFN response. It was shown for several viruses that robust type I IFN responses require this positive feedback loop via the IFNAR. Recently, we showed that infection of IFNAR knockout mice with the orthomyxovirus Thogoto virus lacking the ML open reading frame (THOV(ML-)) results in the expression of unexpected high amounts of type I IFN. To investigate if IFNAR-independent IFN responses are unique for THOV(ML-), we performed infection experiments with several negative-strand RNA viruses using different routes and dosages for infection. A variety of these viruses induced type I IFN responses IFNAR-independently when using the intraperitoneal (i.p.) route for infection. In vitro studies demonstrated that myeloid dendritic cells (mDC) are capable of producing IFNAR-independent IFN-α responses that are dependent on the expression of the adaptor protein mitochondrial antiviral-signalling protein (MAVS) whereas pDC where entirely depending on the IFNAR feedback loop in vitro. Thus, depending on dose and route of infection, the IFNAR feedback loop is not strictly necessary for robust type I IFN expression and an IFNAR-independent type I IFN production might be the rule rather than the exception for infections with numerous negative-strand RNA viruses.

中文翻译：

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I型干扰素受体非依赖性干扰素-α在感染多种负链RNA病毒后的诱导作用

I 型干扰素 (IFN) 是抵御病毒感染的第一道防线。感染后，第一小波早期 I 型 IFN，主要是 IFN-β，特别是 IFN-α 4，被诱导并与 I 型 IFN 受体 (IFNAR) 结合以放大 IFN 反应。对几种病毒表明，稳健的 I 型 IFN 反应需要通过 IFNAR 的这种正反馈回路。最近，我们发现正粘病毒感染 IFNAR 基因敲除小鼠缺乏 ML 开放阅读框 (THOV(ML-)) 的 Thogoto 病毒导致意外大量 I 型干扰素的表达。为了研究独立于 IFNAR 的 IFN 反应是否对 THOV(ML-) 是唯一的，我们使用不同的感染途径和剂量对几种负链 RNA 病毒进行了感染实验。当使用腹膜内 (ip) 途径感染时，多种这些病毒独立地诱导 I 型 IFN 应答 IFNAR。体外研究表明，髓样树突细胞 (mDC) 能够产生不依赖于 IFNAR 的 IFN-α 反应，这些反应依赖于衔接蛋白线粒体抗病毒信号蛋白 (MAVS) 的表达，而 pDC 则完全依赖于 IFNAR 反馈回路体外. 因此，根据感染的剂量和途径，IFNAR 反馈回路对于稳定的 I 型 IFN 表达并不是绝对必要的，并且不依赖于 IFNAR 的 I 型 IFN 产生可能是规则而不是许多负链 RNA 病毒感染的例外.