Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Infect Genet Evol. 2011 Oct;11(7):1805-10. doi: 10.1016/j.meegid.2011.06.022. Epub 2011 Jul 27.
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.
21 个人类乳头瘤病毒 6 型(HPV 6)全长基因组序列的比较分析:本研究中确定的 18 个序列和核苷酸序列数据库中提供的 3 个序列与 HPV 6 原型分离株的核苷酸相似性超过 98%。全长基因组变异体与原型序列之间的最小和最大基因组距离分别为三个核苷酸取代和 122 个核苷酸取代和三个插入。对早期病毒基因 E7、E1、E2 和 E4、晚期病毒基因 L2 以及三个非经典非编码基因组区域(NNCR)的详细序列分析显示,至少存在四个 E7、十二个 E1、十一个 E2、六个 E4、十一个 L2、两个 NNCR1、两个 NNCR2 和三个 NNCR3 基因组变异体。此外,还鉴定了几个新的、可能重要的氨基酸突变。从病毒基因组序列计算的系统发育树是二分的,将所有分离株分为 HPV 6b(原型)和 HPV 6a/6vc(非原型)遗传谱系。本研究贡献了迄今为止最多的 HPV 6 全长基因组序列,证实 HPV 6 通过编码区的核苷酸(氨基酸)交换和非编码区的额外核苷酸插入/缺失在整个基因组中几乎均等多样化。然而,这种多样化趋势在非编码区 LCR 和 NNCR3 以及早期病毒基因 E4、E5a 和 E5b 中更为明显。