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

点击翻译按钮获取中文摘要

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.