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Synthetic viruses: a new opportunity to understand and prevent viral disease

Nature Biotechnology volume 27, pages 1163–1172 (2009)Cite this article

Abstract

Rapid progress in DNA synthesis and sequencing is spearheading the deliberate, large-scale genetic alteration of organisms. These new advances in DNA manipulation have been extended to the level of whole-genome synthesis, as evident from the synthesis of poliovirus, from the resurrection of the extinct 1918 strain of influenza virus and of human endogenous retroviruses and from the restructuring of the phage T7 genome. The largest DNA synthesized so far is the 582,970 base pair genome of Mycoplasma genitalium, although, as yet, this synthetic DNA has not been 'booted' to life. As genome synthesis is independent of a natural template, it allows modification of the structure and function of a virus's genetic information to an extent that was hitherto impossible. The common goal of this new strategy is to further our understanding of an organism's properties, particularly its pathogenic armory if it causes disease in humans, and to make use of this new information to protect from, or treat, human viral disease. Although only a few applications of virus synthesis have been described as yet, key recent findings have been the resurrection of the 1918 influenza virus and the generation of codon- and codon pair–deoptimized polioviruses.

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Figure 1: Comparison of lethality in mice infected with select 1918 and modern human H1N1 influenza A (Tx/91) reassortant viruses.
Figure 2: The poliovirus genome and the effect of codon bias.
Figure 3: The codon pair bias (CPB) score for each of the 14,795 annotated human genes was calculated4.

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Acknowledgements

We are indebted to our colleagues who have participated in the work described here and who have in part edited the manuscript, particularly A. Paul and B. Futcher, and we thank J. Shendure, L. Steward and A.B. Burgin for information provided. The work described here was supported partially by US National Institutes of Health (NIH) grants AI075219 and AI15122 and contract N65236 from the US Defense Advanced Research Project Agency to E.W.; and partially by the intramural research program of the NIH and the National Institute of Allergies and Infectious Diseases (NIAID). The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the funding agency.

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  1. Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA

    Eckard Wimmer & Steffen Mueller

  2. Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.,

    Terrence M Tumpey

  3. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Jeffery K Taubenberger

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Correspondence to Eckard Wimmer.

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Wimmer, E., Mueller, S., Tumpey, T. et al. Synthetic viruses: a new opportunity to understand and prevent viral disease. Nat Biotechnol 27, 1163–1172 (2009). https://doi.org/10.1038/nbt.1593

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