Cryo-electron tomography to study viral infection

Developments in cryo-electron microscopy (cryo-EM) have been interwoven with the study of viruses ever since its first applications to biological systems. Following the success of single particle cryo-EM in the last decade, cryo-electron tomography (cryo-ET) is now rapidly maturing as a technology and catalysing great advancement in struc-tural virology as its application broadens. In this review, we provide an overview of the use of cryo-ET to study viral infection biology, discussing the key workflows and strat-egies used in the field. We highlight the vast body of studies performed on purified viruses and virus-like particles (VLPs), as well as discussing how cryo-ET can character-ise host-virus interactions and membrane fusion events. We further discuss the import-ance of in situ cellular imaging in revealing previously unattainable details of infection and highlight the need for validation of high-resolution findings from purified ex situ systems. We give perspectives for future developments to achieve the full potential of cryo-ET to characterise the molecular processes of viral infection.