title: 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 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.
authors: Jake Gittlen Cancer Research Foundation, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. nmc4@psu.edu
authors: Nancy M
authors: NM
authors: Cladel
authors: Lynn R
authors: LR
authors: Budgeon
authors: Jiafen
authors: J
authors: Hu
authors: Karla K
authors: KK
authors: Balogh
authors: Neil D
authors: ND
authors: Christensen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003062:Codon; D012777:Cottontail rabbit papillomavirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D005814:Genes, Viral; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics*; D009857:Oncogenes; D010212:Papilloma / Q000821:virology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology*; D011817:Rabbits
chemical_list: D003062:Codon; C469554:E6 protein, Cottontail rabbit papillomavirus; C079183:E7 protein, cottontail rabbit papillomavirus; D009856:Oncogene Proteins, Viral