The capacity of zoonotic RNA viruses to emerge as major agents of human disease can appear limitless. Current intervention strategies have demonstrated limited success. Rapid, innovative and effective solutions are needed to reduce the apparently accelerating process of zoonotic disease emergence. We will study the following zoonotic viruses with epidemic potential in Europe: influenza virus, hepatitis E virus, viruses of the Japanese encephalitis serocomplex and lyssaviruses. These diverse viruses arise from the main reservoirs and vectors of potentially emerging viral diseases and use the three major routes of transmission: respiratory, faecal-oral and vector borne. Inter-disciplinary studies will generate valuable data on patterns of crossing the species barrier, transmission and disease emergence, including ecological and anthropological factors which determine virus availability and opportunities for exposure and infection. We will unravel the complex biological interactions between the virus and the recipient hosts that drive the viral adaptation and elucidate the factors determining the ability of the viruses to spread to and between humans (including pandemic spread). Furthermore, immune mechanisms of protection and novel prevention strategies will be investigated. Data will be compiled in a unique and freely accessible data-sharing platform to build a framework for analysing the drivers of pathogen emergence. Modelling, building on the analysis of key data, will focus on the extent to which pathogen trajectories are predictable and will identify high-risk situations and environments. This will allow improvement of disease surveillance, control, preparedness and intervention. Training in leading European Universities, as well as exchanges of approaches and data sharing with national and international health organizations will strengthen European position in this global challenge.