Adding the third dimension to virus life cycles: Three-dimensional reconstruction of icosahedral viruses from cryo-electron micrographs

Viruses are cellular parasites. The linkage between viral and host function s makes the study of a viral life cycle an important key to cellular functi ons. A deeper understanding of many aspects of viral life cycles has emerge d from coordinated molecular and structural studies carried out with a wide range of viral pathogens. Structural studies of viruses by means of cryo-e lectron microscopy and three-dimensional image reconstruction methods have grown explosively in the last decade. Here we review the use of cryo-electr on microscopy for the determination of the structures of a number of icosah edral viruses. These studies span more than 20 virus families. Representati ve examples illustrate the rise of moderate- to low-resolution (7- to 35-An gstrom) structural analyses to illuminate functional aspects of viral life cycles including host recognition, viral attachment, entry, genome release viral transcription, translation, proassembly, maturation, release, and tra nsmission, as well as mechanisms of host defense. The success of cryo-elect ron microscopy in combination with three-dimensional image reconstruction f or icosahedral viruses provides a firm foundation Sol future explorations o f more-complex viral pathogens, including the vast number that are nonspher ical or nonsymmetrical.