Jane Flint - Principles of Virology

The detailed views of nonenveloped virus particles provided by X-ray crystallography emphasize just how well these protein shells provide protection of the genome during passage from one host cell or organism to another. They have also identified several mechanisms by which identical or nonidentical subunits can interact to form icosahedrally symmetric structures, and protein-protein interactions that stabilize larger virus particles with icosahedral symmetry. More-elaborate virus particles, which may contain additional protein layers, a lipid envelope carrying viral proteins, and enzymes or other proteins necessary to initiate the infectious cycle, pose greater challenges to the structural biologist. Indeed, for many years we possessed only schematic views of these structures, deduced from negative-contrast electron microscopy and biochemical or genetic methods of analysis. In previous editions, we noted the power and promise of continuing refinements in methods of cryo-EM (or cryo-electron tomography), image reconstruction, and difference imaging. These techniques have attained atomic- or near-atomic-level resolution, providing remarkable views of large viruses with multiple components, viral envelopes, and, in some cases, the organization of genomes within particles. The structural descriptions of ever-increasing numbers of viruses representing diverse families have also allowed unique insights into evolutionary relationships among seemingly disparate viruses or viral proteins.

These extraordinary advances notwithstanding, important challenges remain, most obviously the visualization of structures that do not exhibit simple symmetry (or are not constructed from components that do). These structures include many genomes and the particles of some large viruses (e.g., poxviruses). The giant viruses, such as mimiviruses and pithoviruses, some with particles so large that they can be seen by light microscopy, also pose new technical challenges and intimate that unanticipated structural principles remain to be elucidated.

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The first experimental measurement of the high internal pressure within a human virus capsid.

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Theoretical principles of quasiequivalence and triangulation number for construction of icosahedral virus particles.

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The classic proposal that viruses are built from identical subunits (for genetic economy) arranged with helical or platonic polyhedral symmetry.

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First X-ray crystal structure of an icosahedral virus and identification of the β-barrel jelly roll topology. Note the high resolution achieved even more than 40 years ago!

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The first three-dimensional structures of human viruses.

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A milestone in cryo-EM of virus particles, a 3.6-Å resolution structure of human adenovirus type 5, a large virus particle that includes several stabilizing proteins.

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This < 10-Å resolution cryo-EM structure revealed the organization of transmembrane segments of the viral glycoproteins and contacts between the capsid and glycoproteins.

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The first structure of an internal viral protein reported.

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Insights into the mechanism of action of a viroporin from structural biology.

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An important generalization and extension of the principle of quasiequivalence.

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An early example of application of mass spectrometry to virus particles.

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X-ray crystal structure of the external domain of this glycoprotein, the first to be determined.