Synonymous codon changes in the oncogenes of the cottontail rabbit papillomavirus lead to increased oncogenicity and immunogenicity of the virus.
Synonymous codon changes in the oncogenes of the cottontail rabbit papillomavirus lead to increased oncogenicity and immunogenicity of the virus.
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DOI：
10.1016/j.virol.2013.01.005
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发表时间：
2013-04-10
期刊：
影响因子：
3.7
通讯作者：
Christensen ND
中科院分区：
文献类型：
--
作者：
Cladel NM;Budgeon LR;Hu J;Balogh KK;Christensen ND
乳头瘤病毒相对于宿主使用罕见的密码子。其原因尚不完全清楚，但在假设中有一种概念，即罕见的密码子导致蛋白质产量低，这使病毒能够逃脱免疫监视。我们改变了棉尾兔乳头瘤病毒的致癌基因E6和E7的罕见密码子，使它们更像哺乳动物，并在体内动物模型中测试了突变基因组。当蛋白质的氨基酸序列保持不变时，一些改变的基因组的致癌潜力显著增加。此外，随着密码子数目的增加，免疫原性也随着自发回归的增加而增加。这项工作表明，密码子的使用可能会以影响疾病结果的方式改变蛋白质的产生，并且在分析感染因子的遗传变异及其与疾病的关联时，应该包括对同义密码子的评估。
Papillomaviruses use rare codons with respect to the host. The reasons for this are incompletely understood but among the hypotheses is the concept that rare codons result in low protein production and this allows the virus to escape immune surveillance. We changed rare codons in the oncogenes E6 and E7 of the cottontail rabbit papillomavirus to make them more mammalian-like and tested the mutant genomes in our in vivo animal model. While the amino acid sequences of the proteins remained unchanged, the oncogenic potential of some of the altered genomes increased dramatically. In addition, increased immunogenicity, as measured by spontaneous regression, was observed as the numbers of codon changes increased. This work suggests that codon usage may modify protein production in ways that influence disease outcome and that evaluation of synonymous codons should be included in the analysis of genetic variants of infectious agents and their association with disease.
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DOI：
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作者：
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