Despite of intensive research the last decades, viral infection still represents a serious threat to human health. One crucial aspect of the defence against viral infection is the activation of the host innate immune response. Recent advances have highlighted the crucial role of the RIG-I receptor in triggering IFN synthesis upon virus infections. This virus sensing pathway mediated by RIG-I is crucial for successful host defence against negative stranded RNA viruses infection such as influenza virus. Influenza viruses are common pathogens responsible for recurrent seasonal respiratory illness and pose a serious threat to public health. Part of the virulence of influenza virus is due to its ability to manipulate the innate immune system. Therefore it is important to understand the mechanism of influenza detection by the RIG-I receptor. Much work in the host and other laboratories has contributed to our understanding of how influenza infection initiates the activation of RIG-I and the identity and properties of RIG-I agonists are well defined. However, the kinetics, subcellular localization and mechanisms underlying this recognition still remain unclear. This question of the localisation of virus recognition and the accessibility of the RIG-I ligand is stressed by the subcellular site of virus replication. For example, the replication cycle of influenza virus occurred in the nucleus of infected cells. Therefore it is quite puzzling how RIG-I that has been described to be a cytoplasmic receptor could be able to interact with the viral genome. The overall goal of this project is to develop a non-invasive technique that allows visualization and localization of influenza nucleic acid replication to analyze its detection by the RIG-I innate immune receptor in living cells. Documenting the spatiotemporal detection of influenza genome will certainly improve our understanding of the host-defence race.