Codon usage bias of low-risk human papillomavirus types 6 and 11

Low-risk human papillomaviruses HPV-6 and HPV-11 impose a substantial global burden of benign disease. While genomically similar to high-risk HPV types, their codon usage patterns remain uncharacterized. This study systematically deciphers these patterns in HPV-6 and HPV-11. Analysis included 214 HPV-6 and 100 HPV-11 genomes from the NCBI GenBank database. Genomic analysis identified a strong preference for A/U-ending synonymous codons (over 85% of preferred codons) and low GC content at third codon positions (<35%). Relative dinucleotide abundance analysis further revealed underrepresentation of ApA, CpG, and UpC, and overrepresentation of CpA and UpG, which critically shaped synonymous codon selection in both genotypes. While Effective Number of Codons (ENC) values >49 indicated limited overall codon bias, multi-method analyses (Parity Rule 2, ENC-plot, neutrality plot) established natural selection as the dominant evolutionary force over mutational pressure. Despite moderate host adaptation, a strategic mismatch exists between viral codon preferences and human tRNA abundance, potentially moderating translational efficiency to favor immune evasion and persistence. The Relative Codon Deoptimization Index (RCDI) values approaching 2 further support a moderate adaptation to human codon usage patterns. These findings provide crucial insights into the molecular evolution of low-risk HPVs and inform the development of codon-optimized therapeutic strategies, including vaccines targeting pathologies like genital warts and recurrent respiratory papillomatosis.