Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
PLoS One. 2011;6(7):e22414. doi: 10.1371/journal.pone.0022414. Epub 2011 Jul 21.
The DNA genome of a novel HPV genotype, HPV-125, isolated from a hand wart of an immuno-competent 19-year old male was fully cloned, sequenced and characterized. The full genome of HPV-125 is 7,809-bp in length with a GC content of 46.4%. By comparing the nucleotide sequence of the complete L1 gene, HPV-125 is phylogenetically placed within cutaneotrophic species 2 of Alphapapillomaviruses, and is most closely related to HPV-3 and HPV-28. HPV-125 has a typical genomic organization of Alphapapillomaviruses and contains genes coding for five early proteins, E6, E7, E1, E2 and E4 and two late capsid proteins, L1 and L2. The genome contains two non-coding regions: the first located between the L1 and E6 genes (nucleotide positions 7,137-7,809, length 673-bp) and the second between genes E2 and L2 (nucleotide positions 3,757-4,216, length 460-bp). The E6 protein of HPV-125 contains two regular zinc-binding domains at amino acid positions 29 and 102, whereas the E7 protein exhibits one such domain at position 50. HPV-125 lacks the regular pRb-binding core sequence within its E7 protein. In order to assess the tissue predilection and clinical significance of HPV-125, a quantitative type-specific real-time PCR was developed. The 95% limit-of-detection of the assay was 2.5 copies per reaction (range 1.7-5.7) and the intra- and inter-assay coefficients of variation were 0.47 and 2.00 for 100 copies per reaction, and 1.15 and 2.15 for 10 copies per reaction, respectively. Testing of a representative collection of HPV-associated mucosal and cutaneous benign and malignant neoplasms and hair follicles (a total of 601 samples) showed that HPV-125 is a relatively rare HPV genotype, with cutaneous tropism etiologically linked with sporadic cases of common warts.
一种新型 HPV 基因型 HPV-125 的 DNA 基因组,从一名免疫功能正常的 19 岁男性的手部疣中分离出来,已被完全克隆、测序并进行了特征描述。HPV-125 的全基因组长度为 7809 个碱基对,GC 含量为 46.4%。通过比较完整 L1 基因的核苷酸序列,HPV-125 在系统发生上属于α乳多空病毒属 2 型的皮肤亲嗜性种,与 HPV-3 和 HPV-28 最为密切相关。HPV-125 具有典型的α乳多空病毒基因组结构,包含编码 5 个早期蛋白(E6、E7、E1、E2 和 E4)和 2 个晚期衣壳蛋白(L1 和 L2)的基因。基因组包含两个非编码区:第一个位于 L1 和 E6 基因之间(核苷酸位置 7137-7809,长度 673 个碱基对),第二个位于 E2 和 L2 基因之间(核苷酸位置 3757-4216,长度 460 个碱基对)。HPV-125 的 E6 蛋白在氨基酸位置 29 和 102 处含有两个规则的锌结合结构域,而 E7 蛋白在位置 50 处含有一个这样的结构域。HPV-125 的 E7 蛋白中缺乏规则的 pRb 结合核心序列。为了评估 HPV-125 的组织倾向性和临床意义,开发了一种定量型特异性实时 PCR 方法。该方法的 95%检测限为每个反应 2.5 个拷贝(范围 1.7-5.7),每个反应的内和间变异系数分别为 100 个拷贝时为 0.47 和 2.00,10 个拷贝时为 1.15 和 2.15。对一组代表性的 HPV 相关黏膜和皮肤良性和恶性肿瘤以及毛囊(共 601 个样本)进行检测显示,HPV-125 是一种相对罕见的 HPV 基因型,其皮肤嗜性与常见疣的散发性病例有关。