Pre-vaccination genomic diversity of human papillomavirus genotype 6 (HPV 6): A comparative analysis of 21 full-length genome sequences

• Published in: Infection, genetics and evolution genetics and evolution, 2011-10, Vol.11 (7), p.1805-1810
• Main Authors: Kocjan, Boštjan J., Jelen, Mateja M., Maver, Polona J., Seme, Katja, Poljak, Mario
• Format: Article
• Language: English
• Subjects: amino acids; Base Sequence; Biological and medical sciences; Complete genome; DNA, Viral - genetics; Epidemiology. Vaccinations; General aspects; genes; Genes, Viral; Genetic Variation; Genome, Viral; Genomic diversity; Genomic variant; genotype; HPV 6; Human papillomavirus; Human papillomavirus 6; Human papillomavirus 6 - classification; Human papillomavirus 6 - genetics; Human papillomavirus 6 - immunology; Human papillomavirus 6 - isolation & purification; Humans; Infectious diseases; Medical sciences; Molecular Sequence Data; mutation; nucleotide sequences; Papillomavirus Infections - virology; Papillomavirus Vaccines - genetics; Phylogeny; sequence analysis; Sequence Homology, Nucleic Acid; Viral Proteins - genetics
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2011.06.022

► We determined 18 full-length genome sequences of human papillomavirus type 6 (HPV 6). ► We provide the first comparative analysis of 21 full-length HPV 6 genome sequences. ► Several novel, potentially important mutations were identified. ► The study results support HPV 6 dichotomic phylogeny. ► Selection pressure potential is similar in all regions of the HPV 6 genome. Comparative analysis of 21 full-length genome sequences of human papillomavirus genotype 6 (HPV 6): 18 determined in this study and three sequences available in nucleotide sequence databases, revealed more than 98% nucleotide similarity to the HPV 6 prototype isolate. The minimum and maximum genomic distance between the full-length genomic variants and the prototype sequence was three nucleotide substitutions, and 122 nucleotide substitutions and three insertions, respectively. Detailed sequence analysis of early viral genes E7, E1, E2 and E4, late viral gene L2, and three non-classic non-coding genomic regions (NNCR) revealed the existence of at least four E7, twelve E1, eleven E2, six E4, eleven L2, two NNCR1, two NNCR2, and three NNCR3 genomic variants. In addition, several novel, potentially important amino acid mutations were identified. A phylogenetic tree calculated from viral genome sequences was dichotomic, separating all isolates into HPV 6b (prototypic) and HPV 6a/6vc (non-prototypic) genetic lineages. This study, which contributed the largest number of full-length HPV 6 genome sequences to date, confirmed that HPV 6 diversifies virtually equally across the entire genome by nucleotide (amino acid) exchanges in coding regions and additional nucleotide insertions/deletions in non-coding regions. However, this diversification trend was more evident in non-coding regions LCR and NNCR3 and early viral genes E4, E5a and E5b.