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A model system to study host genome dynamics mediated by integration of non-retroviral RNA virus (NRVINTEGRATIONMODEL)
Start date: Sep 19, 2011, End date: Sep 18, 2013 PROJECT  FINISHED 

"Genome dynamics is known to be affected by abiotic and biotic factors which enrich the diversity among cells and individuals of the same species. Stress induced by pathogens has been demonstrated to impact host genome stability, but little is known about the effect of non-retroviral RNA viruses (NRVs). NRVs carry a RNA genome and no DNA stage is involved during its infection cycle. Therefore, integration of NRVs' sequences into its host genome is not expected. Despite that, integration of a NRV segment into the host genome has been reported in mammals, plants, insects, fungi and bacteria and was suggested to raise new host phenotypes. Additionally, integration of a host segment within a defective NRV's genome has also been reported demonstrating reciprocal sequence exchange between NRV and its host. Although it has been demonstrated that NRV retrotransposition occurs, the nature of that NRV-mediated host divergence is not clear. Here we propose to further investigate the mechanisms and implications of host-genome plasticity due to NRV integration by building a molecular NRV integration model based on the Lymphocytic Choriomeningitis Virus (LCMV), which has been found integrated within its respective hosts genome, the mouse (Mus musculus) as well as the human. This LCMV-based system is design to carry an integration-induced selective marker, which is assumed to enable identification of cells carrying a DNA version of LCMV-derived sequences in vitro and in vivo. Through combining this experimental system with data analysis, it is likely that we'll be able to initiate, select and track such LCMV-derived integration events. The aforementioned system will serve as a model to determine LCMV's integration frequency, mechanisms, as well as possible implications such as somatic and heritable genetic disorders and virus resistance/tolerance phenotype, triggered by non-retroviral RNA viruses' dynamics with their respective host genomes."
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