Structural biology of viruses

Edited by:
  • Wah Chiu,
  • Roger M. Burnett &
  • Robert Garcea
. Published by Oxford University Press, 198 Madison Avenue, New York, New York 10016, USA; 1997. pp.512. $55.00.
Turnip yellow mosaic virus capsid, Nature Struct. Biol . 3, 771–781.

Viruses have probably always been with us, causing spots and runny noses, swellings and fevers, killing us in severe cases and resulting in losses in essential activities such as farming, horticulture and fishing. That such apparently simple organisms — only a few genes-worth in many cases — can cause such havoc testifies to the power of natural selection to produce highly efficient exploiters of ecological niches, in this case limited populations of susceptible cell types capable of supporting multiplication of specific viruses. The challenge is to understand the molecular basis of this specificity and to attempt to use the knowledge to design new anti-viral strategies.

Early structural studies of viruses, whether by electron microscopy or X-ray diffraction, tended to promote a rather static view of virus structure as a robust protein container or capsid protecting a vulnerable genome within, a view enhanced by geometrical descriptions and classifications of subunit architecture. Subsequently a much more dynamic view has emerged with the realization that the capsid must not only assemble in an appropriate manner but also be capable of disassembly in appropriate circumstances, that it must be able to interact with appropriate cell surface receptors and be internalized by one means or another, be transported to an appropriate cellular compartment and in some cases participate in transcriptional activity. Surveillance by the immune system or pressure from prescribed antiviral drugs often rapidly results in the appearance of mutated resistant strains, which can then propagate in susceptible populations.

Much understanding of these multiple facets of viral lifestyle has come from molecular biology combined with structural studies. For smaller viruses, atomic detail has been achieved from X-ray crystallography. For larger multi-shelled viruses and for complexes between viruses and antibodies or receptors, electron cryo-microscopy has provided ever increasing molecular detail. The combination of the two approaches, fitting high resolution X-ray structures of individual components into lower resolution maps derived from microscopy of complexes, has proved particularly informative. Virus particles and their interactions have such a strong architectural aspect that without these structural insights little in the way of detailed functional interpretation could be made. This is the essential starting point for Structural biology of viruses.

The editors have brought together experts in most of the areas mentioned above to produce an authoritative survey of our present understanding of many of the more functional aspects of viral structure. Besides explaining some of the basic principles of virus structure and outlining the methods used to determine structure, the contributions deal with specific viruses for which structural approaches have proved particularly illuminating. Most emphasis is on animal, especially human, viruses but some consideration is given to assembly of bacterial viruses. Small RNA containing viruses — picornaviruses such as common cold and polio — have been closely studied and chapters deal with attachment and cell entry, with antibody mediated neutralization and with conformational transitions in pathogenesis. Other chapters describe influenza, polyoma, adeno, rota, herpes and retro viruses, with concentration on how structural results illuminate functional aspects of the viral life cycle. The final chapters give a sobering account of attempts at rational structure based design of antiviral compounds, indicating how far we still have to go for this approach to be really useful.

Overall the editors are to be congratulated on having achieved a uniformly polished presentation from a wide diversity of authors. There is a helpful amount of cross-referencing between topics and many of the chapters end with a useful summary or forward look to unsolved problems. Inevitably with this sort of production the references are not very up-to-date, with few papers published after 1994 included. Nevertheless the book provides a useful overview for researchers and students and the many so far unanswered questions raised point to an active area of research for some time to come.