Viral infections lead every year to significant losses of human lives, livestock and plant crops, and are responsible for life-threatening pandemics and emerging epidemics, such as infuenza, HIV, ebola or MERS (Middle East Respiratory Syndrome). Viruses are obligatory intracellular pathogens, with a simple RNA- or DNA-based genome, sheltered in a small protein capsid, and hijack the cellular machinery for all stages of their life-cycle.
As in other insects and invertebrates, in the model organism Drosophila melanogaster, the main antiviral defence is the small interference (si)RNA pathway. In addition to RNAi, other pathways also participate in restricting viral infections in invertebrates, but their role and relative importance in complementing the RNAi response is not completely characterized
Previously, the host laboratory identified a putative novel antiviral restriction mechanism in the follicular somatic cells (FC) of the Drosophila ovarioles. The FC’s constitute an epithelial layer that encapsulates the germline and gives rise to the egg shell. Importantly, these are the last layer of somatic tissue blocking transmission of pathogens to the germline, preventing vertical transmission of viruses. The existence of an additional antiviral pathway in this tissue would then provide an extra layer of protection against virus infection for the next generations. With this project, we set out to identify the genes involved in this new pathway, using a combination of unbiased and targeted genetic screens, genomics and cell culture based assays. The combination of these approached allowed us to discard the involvement of additional RNAi pathways in this novel antiviral mechanism, and led to the identification of seven candidate loci, which are undergoing functional testing.
