Virus Attenuation by Genome-Scale Changes in Codon Pair Bias
Abstract
As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific “codon pair bias” provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over- or underrepresented synonymous codon pairs to encode the poliovirus capsid protein. Underrepresented codon pairs caused decreased rates of protein translation, and polioviruses containing such amino acid-independent changes were attenuated in mice. Polioviruses thus customized were used to immunize mice and provided protective immunity after challenge. This “death by a thousand cuts” strategy could be generally applicable to attenuating many kinds of viruses.
- Publication:
-
Science
- Pub Date:
- June 2008
- DOI:
- 10.1126/science.1155761
- Bibcode:
- 2008Sci...320.1784C
- Keywords:
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- VIROLOGY