A cool hybrid approach to the herpesvirus ‘life’ cycle()

Electron cryo tomography (cryoET) is an ideal technique to study virus–host interactions at molecular resolution. Imaging of biological specimens in a frozen-hydrated state assures a close to native environment. Various virus–host cell interactions have been analysed in this way, with the herpesvirus ‘life’ cycle being the most comprehensively studied. The data obtained were further integrated with fluorescence and soft X-ray cryo microscopy data applied on experimental systems covering a wide range of biological complexity. This hybrid approach combines dynamic with static imaging and spans a resolution range from micrometres to angstroms. Along selected aspects of the herpesvirus replication cycle, we describe dedicated combinations of approaches and how subsequent data integration enables insights towards a functional understanding of the underlying processes.