Control of type III interferon expression and Herpes simplex virus type 1 replication by miR-200

干扰素是由细胞释放的对抗病毒的蛋白质。有3种不同类型的干扰素，它们的不同之处在于产生它们的细胞，以及它们活性的病原体。在我们以前的工作中，使用一种新型的基因组筛选，我们表明，导致唇疱疹和其他一些疾病的病毒，单纯疱疹病毒1型（HSV-1），主要是由所谓的III型干扰素（IFN-λ）控制。微小RNA（miRNAs）是细胞内控制蛋白质产生的遗传物质的小片段。在我们最近的工作中，我们应用了另一种类型的基因组筛选，并确定了哪些miRNA对抗HSV-1。在这个项目中，我们将联合收割机结合这两个基因组筛选的结果来研究抗病毒miRNAs是如何工作的。从我们最近进行的其他工作中，我们知道其中之一miR-200会导致IFN-lambda的增加。已知miR-200受一种名为ZEB 1的抑制性蛋白质调控，但也抑制ZEB 1本身。已知miR-200和ZEB 1之间的这种调节反馈回路控制一系列不同的生物学过程，包括正常发育和癌症。在这个项目中，我们将研究miR-200是否通过ZEB 1和IFN-λ抑制HSV-1。如果是这样的话，miRNA在免疫反应、正常发育和癌症之间建立了功能性联系。我们独特的方法将有助于了解抗病毒miRNAs的机制，并可能有助于开发对抗病毒和癌症的新药。

Interferons are proteins that are released by cells to combat viruses. There are 3 different types of interferons which differ by the cells that produce them but also the pathogens against which they are active. In our previous work using a new type of genomic screen we showed that the virus that causes cold sores and some other diseases, Herpes simplex virus type 1 (HSV-1), is mainly controlled by a so-called type III interferon (IFN-lambda). Micro RNAs (miRNAs) are small pieces of genetic material within cells that control which proteins are produced. In our recent work we applied another type of genomic screen and identified which miRNAs combat HSV-1. In this project we will combine the outcome of these two genomic screens to investigate how antiviral miRNAs work. From other work which we recently did we know that one of them, miR-200, leads to an increase of IFN-lambda. miR-200 is known to be regulated by an inhibitory protein called ZEB1, but also inhibits ZEB1 itself. This regulatory feedback loop between miR-200 and ZEB1 is known to control a range of different biological processes, both in normal development and cancer. In this project we will investigate if miR-200 inhibits HSV-1 through ZEB1 and IFN-lambda. If this is the case, miRNA creates a functional link between the immune response, normal development and cancer. Our unique approach will help to understand the mechanisms of antiviral miRNAs and could be instrumental for the development of novel drugs against viruses and cancer.