Synonymous codon changes in the oncogenes of the cottontail rabbit papillomavirus lead to increased oncogenicity and immunogenicity of the virus

Abstract 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 oncoge...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2013-04, Vol.438 (2), p.70-83
Main Authors: Cladel, Nancy M, Budgeon, Lynn R, Hu, Jiafen, Balogh, Karla K, Christensen, Neil D
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cancer
Codon
Codon usage
Cottontail rabbit papillomavirus - genetics
Cottontail rabbit papillomavirus - immunology
Cottontail rabbit papillomavirus - pathogenicity
CRPV
Genes, Viral
Immunogenicity
In vivo model
Infectious Disease
Mutation
Oncogene Proteins, Viral - chemistry
Oncogene Proteins, Viral - genetics
Oncogenes
Papilloma - virology
Papillomavirus
Papillomavirus Infections - immunology
Papillomavirus Infections - virology
Rabbits
Synonymous codons
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Summary:Abstract 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2013.01.005