In vivo effects of miRNAs inthe murine herpesvirus 68 (mHV-68)

Coordinator:		PD Dr. Heiko Adler
Institution:		Helmholtz Zentrum München
Homepage:		www.helmholtz-muenchen.de

Herpesviruses are causing significant morbidity and mortality in the human population. The human gammaherpesviruses Epstein-Barr Virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are associated with a number of tumors and lymphoproliferative disorders. Since pathogenetic studies of human gammaherpesvirus infections are restricted, animal models are of crucial importance. Murine gammaherpesvirus 68 (MHV-68) infection of mice is currently the only small animal model to investigate gammaherpesvirus pathogenesis. It allows to analyze in vivo features of virus-host interactions that are difficult to assess in humans. Recently, it was discovered that viruses, like genomes of eukaryotic cells, encode miRNAs. It was proposed that these miRNAs participate in both lytic and latent infection and may be involved in virus-host interactions. Elucidation of the function of these viral miRNAs will reveal whether they modulate pathogenesis and might also suggest new therapeutic approaches. In this project, we want to investigate the functions of virus-encoded miRNAs during gammaherpesvirus infection using MHV-68 as a model. We plan to analyze the function of the MHV-68 miRNAs in vitro and in vivo. For that purpose, we will construct MHV-68 deletion mutants which lack miRNAs. The analysis of the mutants will allow us to assess the role of the viral miRNAs during the course of the infection.