Abstract
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.
Highlights
Papillomaviruses are double-stranded DNA tumor viruses of about 8 kb
Protein was detected in the positive control and in cells transfected with E7/18 and E7/22 but not in cells transfected with wild type E7 or E7/8 and E7/14 (Fig 2)
All codonmodified genes utilized the same set of E7 primers and probe; E7/ wild type amplification required a slightly modified set. In this analysis, which was conducted in duplicate, we found that TATA-binding protein (TBP) was not stable over time; each analysis included a standard curve to allow for quantitation
Summary
Papillomaviruses are double-stranded DNA tumor viruses of about 8 kb. There are more than 100 human papillomavirus types, some specific for mucosal tissues and others for cutaneous sites. Papillomaviruses use rare codons relative to their hosts [1,2]. The reasons for codon bias are poorly understood. There is a growing recognition that synonymous codon usage is not always neutral [4,5,6]. Many reasons have been posited for codon choice. Control of translation rate and gene expression [7,8]. 2. Control of protein folding [9,10,11]. 4. Tissue specificity requirements [13,14,15]. Selection for translational efficiency [21] and 7. Provision for splicing [22]
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