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  • Review Article
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Physics of viral dynamics

Nature Reviews Physics volume 3, pages 76–91 (2021)Cite this article

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Abstract

Viral capsids are often regarded as inert structural units, but in actuality they display fascinating dynamics during different stages of their life cycle. With the advent of single-particle approaches and high-resolution techniques, it is now possible to scrutinize viral dynamics during and after their assembly and during the subsequent development pathway into infectious viruses. In this Review, the focus is on the dynamical properties of viruses, the different physical virology techniques that are being used to study them, and the physical concepts that have been developed to describe viral dynamics.

Key points

  • Viruses are highly dynamic structures.

  • Physics approaches are well suited to study the mechanisms behind the viral life cycle.

  • New single-particle techniques provide unprecedented insight into viral assembly. These techniques include resistive-pulse sensing, high-speed atomic force microscopy, interferometric scattering, charge-detection mass spectrometry and optical tweezers.

  • Assembly studies of both empty shells and genome-filled shells provide insights into the molecular mechanism and pathways of viral self-assembly.

  • Maturation is a fascinating process in which large structural changes occur in viruses.

  • Closed-shell dynamics includes soft modes and conformational changes.

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Fig. 1: Assembly of empty capsids.
Fig. 2: Assembly around a genome.
Fig. 3: Packaging signals.
Fig. 4: Closed-shell dynamics.

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Acknowledgements

The authors thank C. Knobler for a critical reading of the manuscript, and C. Uetrecht and S. Maity for their input. W.H.R. is supported by a VIDI grant from the Nederlandse Oganizatie voor Wetenschappelijk Onderzoek. R.B. is supported by the NSF-DMR under CMMT grant 1836404.

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Authors and Affiliations

  1. Department of Physics and Astronomy, University of California, Los Angeles, California, USA

    Robijn F. Bruinsma

  2. Fysica van levende systemen, Vrije Universiteit, Amsterdam, the Netherlands

    Gijs J. L. Wuite

  3. Moleculaire Biofysica, Zernike Instituut, Rijksuniversiteit Groningen, Groningen, the Netherlands

    Wouter H. Roos

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Correspondence to Wouter H. Roos.

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G.J.L.W. declares financial interest in fluorescence optical tweezers and acoustic force spectroscopy approaches which are patented and licensed to LUMICKS B.V.

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Glossary

Capsids

Protein shells that surround the viral genome.

Triangulation numbers

Classification system, developed by Caspar and Klug, for icosahedral viruses. T-numbers are integers and contain information on the number of protein subunits that make up a capsid.

Virions

Viral particles, composed of both capsid proteins and the viral genome, that can successfully infect cells.

Kinetic traps

Kinetically trapped assembly intermediates that are dead-end products and do not lead to the formation of correctly assembled viral particles.

Bacteriophage

Also called phages, these are viruses that infect bacteria.

Procapsids

Immature and precursor viral capsid structures of certain viruses.

Host cells

Cells infected by virions.

Archaeal

Next to bacteria and eukaryotes, archaea represent one of the three domains of life.

Prokaryotic

A prokaryote is a single cell organism lacking a nucleus, that is, bacteria or archaea.

Eukaryotic

A eukaryote is an organism built up from eukaryotic cells, that is, from cells that possess a nucleus. Animals, plants and fungi are examples of eukaryotes.

Nucleotides

Building blocks of nucleic acids (of DNA or RNA).

Secondary structure

The set of formed base pairs in a nucleic acid strand; in other words, the set of links between nucleotides in the strand.

PolyU

Nucleic acid strand consisting solely of copies of the uracil (U) nucleotide.

PolyA

Nucleic acid strand consisting solely of copies of the adenine (A) nucleotide.

Langmuir adsorption theory

Model describing key physics of molecular interactions at interfaces.

Gag protein

Group-specific antigen protein. The Gag polyprotein makes up the inner shell of immature retroviral particles, and during maturation Gag is proteolytically cleaved into MA (matrix), CA (capsid) and NC (nucleocapsid) domains leading to the formation of a mature virion.

Nucleocapsid domain

Viral protein coat surrounding the viral genome. One of the three domains resulting from Gag protein cleavage.

Retroviruses

Group of viruses with a viral RNA genome. During infection, DNA is produced using the viral RNA.

Maturation

Process of conformational changes and/or proteolytic cleavage of viral proteins transforming the immature particle into a mature, infectious particle.

Cytoplasmic membrane

Membrane enclosing the cellular cytoplasm. It is the outer membrane of eukaryotic cells and the first cellular contact point for viruses during infection.

Endosome

Intracellular vesicles. Certain viruses are internalized into their host cell in an endosome and subsequently leave this endosome to continue the infectious pathway.

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Bruinsma, R.F., Wuite, G.J.L. & Roos, W.H. Physics of viral dynamics. Nat Rev Phys 3, 76–91 (2021). https://doi.org/10.1038/s42254-020-00267-1

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