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

干扰素是细胞释放出来对抗病毒的蛋白质。有三种不同类型的干扰素不同于产生它们的细胞也不同于它们所对抗的病原体。在我们之前使用一种新型基因组筛选的工作中，我们发现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），主要由所谓的III型干扰素（IFN-lambda）控制。微rna （miRNAs）是细胞内控制蛋白质产生的小块遗传物质。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可以对抗HSV-1。在这个项目中，我们将结合这两个基因组筛选的结果来研究抗病毒mirna是如何工作的。从我们最近做的其他工作中我们知道其中一个，miR-200，会导致IFN-lambda的增加。已知miR-200受一种称为ZEB1的抑制蛋白调控，但也抑制ZEB1本身。已知miR-200和ZEB1之间的这种调节反馈回路在正常发育和癌症中控制着一系列不同的生物过程。在这个项目中，我们将研究miR-200是否通过ZEB1和IFN-lambda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联系。我们独特的方法将有助于理解抗病毒mirna的机制，并可能有助于开发针对病毒和癌症的新型药物。

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.