Chen Zigui, Schiffman Mark, Herrero Rolando, DeSalle Rob, Anastos Kathryn, Segondy Michel, Sahasrabuddhe Vikrant V, Gravitt Patti E, Hsing Ann W, Burk Robert D
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, United States of America.
PLoS One. 2013 Aug 16;8(8):e72565. doi: 10.1371/journal.pone.0072565. eCollection 2013.
The species Alphapapillomavirus 7 (alpha-7) contains human papillomavirus genotypes that account for 15% of invasive cervical cancers and are disproportionately associated with adenocarcinoma of the cervix. Complete genome analyses enable identification and nomenclature of variant lineages and sublineages.
The URR/E6 region was sequenced to screen for novel variants of HPV18, 39, 45, 59, 68, 70, 85 and 97 from 1147 cervical samples obtained from multiple geographic regions that had previously been shown to contain an alpha-7 HPV isolate. To study viral heterogeneity, the complete 8 kb genome of 128 isolates, including 109 sequenced for this analysis, were annotated and analyzed. Viral evolution was characterized by constructing phylogenic trees using maximum-likelihood and Bayesian algorithms. Global and pairwise alignments were used to calculate total and ORF/region nucleotide differences; lineages and sublineages were assigned using an alphanumeric system. The prototype genome was assigned to the A lineage or A1 sublineage.
The genomic diversity of alpha-7 HPV types ranged from 1.1% to 6.7% nucleotide sequence differences; the extent of genome-genome pairwise intratype heterogeneity was 1.1% for HPV39, 1.3% for HPV59, 1.5% for HPV45, 1.6% for HPV70, 2.1% for HPV18, and 6.7% for HPV68. ME180 (previously a subtype of HPV68) was designated as the representative genome for HPV68 sublineage C1. Each ORF/region differed in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1) / noncoding region 2 (NCR2) > upstream regulatory region (URR) > E6 / E7 > E2 / L2 > E1 / L1.
These data provide estimates of the maximum viral genomic heterogeneity of alpha-7 HPV type variants. The proposed taxonomic system facilitates the comparison of variants across epidemiological and molecular studies. Sequence diversity, geographic distribution and phylogenetic topology of this clinically important group of HPVs suggest an independent evolutionary history for each type.
α乳头瘤病毒7型（α-7）包含的人乳头瘤病毒基因型占浸润性宫颈癌的15%，且与宫颈腺癌的关联尤为突出。全基因组分析有助于识别变异谱系和亚谱系并为之命名。
对来自多个地理区域的1147份宫颈样本的URR/E6区域进行测序，以筛查HPV18、39、45、59、68、70、85和97的新型变体，这些样本此前已被证明含有α-7型人乳头瘤病毒分离株。为研究病毒异质性，对128个分离株的完整8kb基因组（包括本次分析测序的109个）进行注释和分析。通过使用最大似然法和贝叶斯算法构建系统发育树来表征病毒进化。使用全局和成对比对来计算总核苷酸差异和开放阅读框/区域核苷酸差异；使用字母数字系统指定谱系和亚谱系。将原型基因组指定为A谱系或A1亚谱系。
α-7型人乳头瘤病毒的基因组多样性在核苷酸序列差异方面为1.1%至6.7%；基因组间成对型内异质性程度在HPV39中为1.1%，HPV59中为1.3%，HPV45中为1.5%，HPV70中为1.6%，HPV18中为2.1%，HPV68中为6.7%。ME180（以前是HPV68的一个亚型）被指定为HPV68亚谱系C1的代表性基因组。每个开放阅读框/区域的序列多样性各不相同，从变化最大到最小依次为：非编码区1（NCR1）/非编码区2（NCR2）>上游调控区（URR）>E6/E7>E2/L2>E1/L1。
这些数据提供了α-7型人乳头瘤病毒变体最大病毒基因组异质性的估计值。所提出的分类系统有助于在流行病学和分子研究中比较变体。这一临床上重要的人乳头瘤病毒组的序列多样性、地理分布和系统发育拓扑结构表明每种类型都有独立的进化史。
