Faculty of Medicine, Institute of Microbiology and Immunology, University of Ljubljana, Ljubljana, Slovenia.
Dermacenter, Ljubljana, Slovenia.
PLoS One. 2021 May 6;16(5):e0249829. doi: 10.1371/journal.pone.0249829. eCollection 2021.
To determine the prevalence, viral load, tissue tropism, and genetic variability of novel human papillomavirus (HPV) type 179, which is etiologically associated with sporadic cases of common warts in immunocompromised patients, and phylogenetically related HPV types 135 and 146.
The representative collection of 850 HPV-associated clinical samples (oral/nasopharyngeal/anal, archival specimens of oral/oropharyngeal/conjunctival/cervical/skin cancer, benign lesions of the larynx/conjunctiva/skin, and eyebrows), obtained from immunocompetent individuals, was tested for the presence of HPV179, HPV135, and HPV146 using type-specific real-time PCRs. To assess the genetic diversity of the HPVs investigated in the non-coding long control region (LCR), several highly sensitive nested PCR protocols were developed for each HPV type. The genetic diversity of HPV179 was additionally determined in 12 HPV179 isolates from different anatomical sites of an only immunocompromised patient included in the study.
HPV179, HPV135, and HPV146 were detected in 1.4, 2.0, and 1.5% of the samples tested, respectively, with no preference for cutaneous or mucosal epithelial cells. One (with five single nucleotide polymorphisms; SNPs), four (with one to six SNPs), and four (with one to eight SNPs) genetic variants of HPV179, HPV135, and HPV146, respectively, were identified among eligible samples. HPV179 isolates from the immunocompromised patient exhibited the identical LCR nucleotide sequence, suggesting that HPV179 can cause generalized HPV infections.
HPV179, HPV135, and HPV146 have a mucocutaneous tissue tropism and are associated with sporadic infections in immunocompromised and immunocompetent individuals. Because the majority of mutations were found outside the major functional domains of the respective LCRs, we assume that HPV179, HPV135, and HPV146 genetic variants pathogenically do not differ from their prototypes. In addition, no association was found between specific HPV179, HPV135, and HPV146 genetic variants and anatomical sites of infection and/or specific neoplasms.
确定新型人乳头瘤病毒(HPV)179 的流行率、病毒载量、组织嗜性和遗传变异性,该病毒与免疫功能低下患者的散发性寻常疣有关,与进化上相关的 HPV 135 和 146 有关。
使用针对 HPV 179、HPV 135 和 HPV 146 的型特异性实时 PCR 检测来自免疫功能正常个体的 850 份 HPV 相关临床样本(口腔/鼻咽/肛门,口腔/口咽/结膜/宫颈/皮肤癌存档标本、喉/结膜/皮肤良性病变和眉毛)中是否存在 HPV179、HPV135 和 HPV146。为了评估在所研究的非编码长控制区(LCR)中 HPV 的遗传多样性,为每种 HPV 类型开发了几个高度敏感的嵌套 PCR 方案。在研究中包括的一名免疫功能低下的患者的不同解剖部位的 12 个 HPV179 分离株中进一步确定了 HPV179 的遗传多样性。
在测试的样本中,分别检测到 HPV179、HPV135 和 HPV146 的 1.4%、2.0%和 1.5%,无皮肤或粘膜上皮细胞偏好。在合格样本中分别鉴定出 HPV179、HPV135 和 HPV146 的一种(具有五个单核苷酸多态性;SNP)、四种(具有一个至六个 SNP)和四种(具有一个至八个 SNP)遗传变异。来自免疫功能低下患者的 HPV179 分离株显示出相同的 LCR 核苷酸序列,表明 HPV179 可引起全身性 HPV 感染。
HPV179、HPV135 和 HPV146 具有粘膜皮肤组织嗜性,并与免疫功能低下和免疫功能正常个体的散发性感染有关。由于大多数突变发生在各自 LCR 的主要功能域之外,因此我们假设 HPV179、HPV135 和 HPV146 的遗传变异在病理学上与原型没有区别。此外,没有发现特定的 HPV179、HPV135 和 HPV146 遗传变异与感染和/或特定肿瘤的特定解剖部位之间存在关联。