CRPV genomes with synonymous codon optimizations in the CRPV E7 gene show phenotypic differences in growth and altered immunity upon E7 vaccination.

CRPV genomes with synonymous codon optimizations in the CRPV E7 gene show phenotypic differences in growth and altered immunity upon E7 vaccination.
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DOI:
10.1371/journal.pone.0002947
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发表时间:
2008-08-13
期刊:
影响因子:
3.7
通讯作者:
Christensen ND
Christensen ND
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cladel NM;Hu J;Balogh KK;Christensen ND

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乳头瘤病毒使用相对于其宿主罕见的密码子。最近的研究表明,当病毒基因中的同义密码子与表达蛋白质的细胞的密码子相匹配时,病毒基因中的同义密码子变化可导致蛋白质产量增加。我们的理论是,通过将选定的病毒基因的密码子与宿主的密码子相匹配,可以增强病毒的免疫原性。我们在这里报告,同义密码子的E7癌基因的变化是容忍的背景下,棉尾兔乳头瘤病毒(CRPV)的基因组。乳头状瘤的生长速度不同,这取决于所做的改变,表明同义密码子不一定是中性的。用野生型E7 DNA免疫产生了显著的保护作用,使其免受野生型和密码子修饰的基因组的后续攻击。对于含有最多同义密码子变化的基因组,生长的减少最为显着。
Papillomaviruses use rare codons relative to their hosts. Recent studies have demonstrated that synonymous codon changes in viral genes can lead to increased protein production when the codons are matched to those of cells in which the protein is being expressed. We theorized that the immunogenicity of the virus would be enhanced by matching codons of selected viral genes to those of the host. We report here that synonymous codon changes in the E7 oncogene are tolerated in the context of the cottontail rabbit papillomavirus (CRPV) genome. Papilloma growth rates differ depending upon the changes made indicating that synonymous codons are not necessarily neutral. Immunization with wild type E7 DNA yielded significant protection from subsequent challenge by both wild type and codon-modified genomes. The reduction in growth was most dramatic with the genome containing the greatest number of synonymous codon changes.
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