Cryo-electron microscopy for the study of virus assembly


Although viruses are extremely diverse in shape and size, evolution has led to a limited number of viral classes or lineages, which is probably linked to the assembly constraints of a viable capsid. Viral assembly mechanisms are restricted to two general pathways, (i) co-assembly of capsid proteins and single-stranded nucleic acids and (ii) a sequential mechanism in which scaffolding-mediated capsid precursor assembly is followed by genome packaging. Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), which are revolutionizing structural biology, are central to determining the high-resolution structures of many viral assemblies as well as those of assembly intermediates. This wealth of cryo-EM data has also led to the development and redesign of virus-based platforms for biomedical and biotechnological applications. In this Review, we will discuss recent viral assembly analyses by cryo-EM and cryo-ET showing how natural assembly mechanisms are used to encapsulate heterologous cargos including chemicals, enzymes, and/or nucleic acids for a variety of nanotechnological applications.

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Fig. 1: Overview of cryo-EM and cryo-ET workflow, from data acquisition to 3D model.
Fig. 2: Viral lineages and their representative folds and capsid structures.
Fig. 3: Co-assembly of CPs and viral single-stranded genome.
Fig. 4: Scaffolding protein-assisted capsid assembly.
Fig. 5: Assembly of dsRNA viruses assisted by a permanent scaffold protein shell.
Fig. 6: IBDV capsid assembly model.
Fig. 7: Cryo-ET of pleomorphic viruses and intracellular viral assembly.
Fig. 8: Assembly strategies to develop hybrid P22 and CCMV.


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We apologize to our colleagues with outstanding contributions who were not mentioned due to space limitations. The authors thank J.L. Carrascosa, C. San Martín and J.M. Rodríguez for critical reading of the manuscript, and C. Mark for editorial assistance. This work was supported by grants from the Spanish Ministry of Economy and Competitivity (BFU2017-88736-R) and the Comunidad Autónoma de Madrid (P2018/NMT-4389) to J.R.C.

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Luque, D., Castón, J.R. Cryo-electron microscopy for the study of virus assembly. Nat Chem Biol 16, 231–239 (2020).

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