Virus Attenuation by Genome-Scale Changes in Codon Pair Bias

by: Robert J Coleman, Dimitris Papamichail, Steven Skiena, Bruce Futcher, Eckard Wimmer, Steffen Mueller

Science, Vol. 320, No. 5884. (27 June 2008), pp. 1784-1787.

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摘要

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. 10.1126/science.1155761

@article{citeulike:2937482, 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. 10.1126/science.1155761}, author = {Coleman, Robert J. and Papamichail, Dimitris and Skiena, Steven and Futcher, Bruce and Wimmer, Eckard and Mueller, Steffen }, citeulike-article-id = {2937482}, doi = {http://dx.doi.org/10.1126/science.1155761}, journal = {Science}, keywords = {replication, vaccine}, month = {June}, number = {5884}, pages = {1784--1787}, posted-at = {2008-06-30 11:10:35}, priority = {2}, title = {Virus Attenuation by Genome-Scale Changes in Codon Pair Bias}, url = {http://dx.doi.org/10.1126/science.1155761}, volume = {320}, year = {2008} }

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TY - JOUR ID - citeulike:2937482 L3 - citeulike-article-id:2937482 N2 - 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. 10.1126/science.1155761 IS - 5884 JF - Science EP - 1787 TI - Virus Attenuation by Genome-Scale Changes in Codon Pair Bias VL - 320 SP - 1784 KW - replication KW - vaccine AU - Coleman, Robert AU - Papamichail, Dimitris AU - Skiena, Steven AU - Futcher, Bruce AU - Wimmer, Eckard AU - Mueller, Steffen PY - 2008/06/27/ UR - http://dx.doi.org/10.1126/science.1155761 ER -

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