Towards an atomic resolution understanding of the influenza virus replication machinery

The influenza polymerase transcribes and replicates the viral RNA genome within the context of a ribonucleoprotein complex that has been hitherto remarkably intractable to structural analysis. In the last two years, crystal structures of independent domains covering roughly half of the heterotrimeric polymerase have been determined. These include the cap-binding and endonuclease domains, critical for the unique cap-snatching mechanism of mRNA transcription, and the major inter-subunit interfaces. In addition, a cryo-electron microscopy structure of the entire ribonucleoprotein complex has been determined opening the way to the construction of a quasi-atomic model of the influenza replication machinery. These results provide the first detailed structure–function insights into polymerase assembly, transcription and host adaptation and will have an impact on anti-influenza drug design.