microRNA regulation of virus gene expression

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Background. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at a post-transcriptional level. miRNAs play a central role in regulating a wide variety of biological processes and as such dysregulation of miRNA expression has been implicated in many human diseases. We have exciting preliminary data, using miRNA profiling, suggesting that host miRNA expression can be dysregulated during the KSHV lytic replication cycle. Therefore, miRNA dysregulation contributes a key role in mediating viral replication, pathogenesis and tumourigenesis.Objectives. The aim of this project is to determine how virus-mediated manipulation of host cell miRNAs regulates both virus and host cell gene expression during virus infection. Moreover, the project has potential to identify novel host cell restriction factors which prevent herpesvirus replication, highlighting potential therapeutic approaches for the treatment of this important family of viruses.Novelty. This project is highly novel. An emerging area of research suggests that manipulation of miRNA expression can have fundamental effects on host cell gene expression. The project will therefore investigate novel mechanisms utilised by the virus to regulate host cell gene expression which can dictate how the virus and host cell transcriptome is regulated to benefit virus replication.Timeliness. The project is timely as this is an emerging area of research. miRNAs are key regulators of gene expression and aberrant expression of miRNAs is increasingly being associated with human disease.Experimental Approach. The project utilises a multidisiplinary approach and cutting-edge methodology including miRNA seq, bioinformatic analysis, imaging and cell biology.