Antivirally active factors of the type I interferon systems of small mammals

干扰素（IFN）系统代表了对抗入侵病毒的重要物种屏障和控制实例。细胞可以通过病原体识别受体（PRR）来感知病毒感染，并通过合成和分泌IFN-α/β来应答。IFN与周围细胞上的同源受体的结合导致超过350种IFN刺激基因（ISG）的表达。几种ISG产品具有抗病毒特性，从而控制病毒复制和传播。蝙蝠和其他小型哺乳动物的干扰素系统的特点是生病至今，虽然它被怀疑是主要负责这些动物的能力，作为人畜共患病毒的水库。为了填补这一知识空白，我们在第一个资助期内建立了分子工具，并开始产生鼠耳蝠全基因组、病毒和IFN应答转录组。从该物种中，我们还克隆，表达和表征了主要的PRR和ISG，即RIG-I和Mx 1，分别，以及来自另外六种蝙蝠和五种啮齿动物的Mx 1蛋白。我们的初步结果表明，这些关键的干扰素因子是功能性的，但可以不同于他们的人类people.Having现在建立了一个坚实的实验基础，我们希望在我们的成就在第二个资助期。我们的目标是（i）完成病毒和干扰素诱导的蝙蝠转录组，（ii）与相应的人类转录组进行比较，并评估和表征有趣的命中，（iii）进行深入比较RIG-I和Mx蛋白的人类，蝙蝠和啮齿动物，和（iv）定义这些关键干扰素因子的抗病毒谱。IFN系统的相似性和差异的识别和表征将有助于理解为什么水库物种比人类更好地应对病毒。

The interferon (IFN) system represents an important species barrier and control instance against invading viruses. Cells can sense viral infection by means of pathogen recognition receptors (PRRs), and respond by synthesizing and secreting IFN-alpha/beta. The binding of IFNs to their cognate receptor on surrounding cells leads to the expression of more than 350 IFN-stimulated genes (ISGs). Several ISG products possess antiviral properties, thus controlling viral replication and spread. The IFN system of bats and other small mammals is ill characterized so far, although it is suspected to be mainly responsible for the ability of these animals to serve as reservoirs for zoonotic viruses. To fill this knowledge gap, we established during the first funding period molecular tools and started generating genome-wide, virus- and IFN-responsive transcriptomes of Myotis daubentonii. From that species we also cloned, expressed, and characterized the main PRRs and ISGs, namely RIG-I and Mx1, respectively, as well as Mx1 proteins from six additional bat and five rodent species. Our preliminary results show that these key IFN factors are functional, but can differ from their human counterparts.Having now established a firm experimental basis, we want to build on our achievements in the second funding period. Our goals are to (i) complete the virus- and IFN-induced transcriptomes of bats, (ii) compare with the corresponding human transcriptomes and evaluate and characterize interesting hits, (iii) perfom an in-depth comparison of RIG-I and Mx proteins of humans, bats, and rodents, and (iv) define the antiviral spectrum of these key IFN factors. Identification and characterization of similarities and differences in the IFN systems will help to understand why reservoir species are better coping with viruses than humans.