Codon usage roles in human papillomavirus

Abstract

Human papillomavirus (HPV) genomes, similar to other virus genomes, frequently have a G + C content significantly different from their host species. The HPV genomes show a strong codon usage bias to 18 codons, with 14 showing T at the third position amongst degenerately encoded amino acids. The codon usage pattern in HPV genome plays an important role, which regulates low or non-translational expression of the viral capsid genes and results in very weak protein expression of oncogenes in a wide range of mammalian cells. Codon modification has been proved to be a powerful technology to overcome the translational blockage and weak expression of both HPV capsid genes and oncogenes in different expression systems. Furthermore, keratinocytes are the host cells of HPV infection; the codon usage in HPV capsid genes matches available aminoacyl-tRNAs in differentiated keratinocytes to modulate their protein expression. HPV DNA vaccines with codon optimization have been shown to have higher immunogenicity and induce both strong cellular and humoral responses in animal models, which may be a promising form of therapeutic HPV vaccines.