Influenza A virus is a global public health threat. It is responsible for seasonal epidemics and occasional pandemics of respiratory disease showing substantial morbidity and mortality in humans and a considerable financial burden worldwide. Although vaccines and antiviral compounds against influenza A virus are available, the protection that they provide is limited owing to the high mutation rates of the virus, resulting in continuous changes in antigenicity. At the molecular level, the dominant source of mutations is the error-prone viral RNA polymerase, which is the protein complex responsible for replicating and transcribing the viral genome. Due to its major role on the high antigenic variation of the virus, the RNA polymerase has become an important target for antiviral therapies that seek to alter its fidelity. The main objective of this project is to address the molecular mechanisms that govern the operational dynamics of influenza A RNA polymerase within the context of the viral genome.