Key Laboratory of Bio‑Resources and Eco‑Environment, Ministry of Education, Institute of Medical Genetics, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, P.R. China.
Mol Med Rep. 2018 May;17(5):7131-7141. doi: 10.3892/mmr.2018.8743. Epub 2018 Mar 14.
Globally, human papillomavirus (HPV)‑56 accounts for a small proportion of all high‑risk HPV types; however, HPV‑56 is detected at a higher rate in Asia, particularly in southwest China. The present study analyzed polymorphisms, intratypic variants, and genetic variability in the long control regions (LCR), E6, E7, and L1 of HPV‑56 (n=75). The LCRs, E6, E7 and L1 were sequenced using a polymerase chain reaction and the sequences were submitted to GenBank. Maximum‑likelihood trees were constructed using Kimura's two‑parameter model, followed by secondary structure analysis and protein damaging prediction. Additionally, in order to assess the effect of variations in the LCR on putative binding sites for cellular proteins, MATCH server was used. Finally, the selection pressures of the E6‑E7 and L1 genes were estimated. A total of 18 point substitutions, a 42‑bp deletion and a 19‑bp deletion of LCR were identified. Some of those mutations are embedded in the putative binding sites for transcription factors. 18 single nucleotide changes occurred in the E6‑E7 sequence, 11/18 were non‑synonymous substitutions and 7/18 were synonymous mutations. A total 24 single nucleotide changes were identified in the L1 sequence, 6/24 being non‑synonymous mutations and 18/24 synonymous mutations. Selective pressure analysis predicted that the majority of mutations of HPV‑56 E6, E7 and L1 were of positive selection. The phylogenetic tree demonstrated that the isolates distributed in two lineages. Data on the prevalence and genetic variation of HPV‑56 types in southwest China may aid future studies on viral molecular mechanisms and contribute to future investigations of diagnostic probes and therapeutic vaccines.
全球范围内,人乳头瘤病毒(HPV)-56 在所有高危 HPV 型别中仅占一小部分;然而,HPV-56 在亚洲的检出率较高,尤其是在中国西南部。本研究分析了 HPV-56(n=75)的长控制区(LCR)、E6、E7 和 L1 中的多态性、同型内变体和遗传变异。使用聚合酶链反应对 LCRs、E6、E7 和 L1 进行测序,并将序列提交至 GenBank。使用 Kimura 的双参数模型构建最大似然树,随后进行二级结构分析和蛋白损伤预测。此外,为了评估 LCR 变异对细胞蛋白可能结合位点的影响,使用了 MATCH 服务器。最后,估计了 E6-E7 和 L1 基因的选择压力。共鉴定出 18 个点突变、42bp 缺失和 LCR 19bp 缺失。其中一些突变嵌入了转录因子的潜在结合位点。E6-E7 序列中发生了 18 个单核苷酸变化,其中 11/18 为非同义取代,7/18 为同义突变。L1 序列中总共鉴定出 24 个单核苷酸变化,其中 6/24 为非同义突变,18/24 为同义突变。选择压力分析预测 HPV-56 E6、E7 和 L1 的大多数突变均为正选择。系统发育树表明,分离株分布在两个谱系中。中国西南部 HPV-56 型的流行率和遗传变异数据可能有助于未来对病毒分子机制的研究,并为未来诊断探针和治疗性疫苗的研究做出贡献。