Cochicho Daniela, Nunes Alexandra, Gomes João Paulo, Martins Luís, Cunha Mário, Medeiros-Fonseca Beatriz, Oliveira Paula, Bastos Margarida M S M, Medeiros Rui, Mendonça Joana, Vieira Luis, Gil da Costa Rui M, Felix Ana
NOVA Medical School-Universidade NOVA de Lisboa, NOVA University, 1169-056 Lisbon, Portugal.
Virology Laboratory from Clinical Pathology Department, Portuguese Institute of Oncology Francisco Gentil (IPOLFG), 1099-023 Lisbon, Portugal.
Int J Mol Sci. 2022 Oct 15;23(20):12371. doi: 10.3390/ijms232012371.
The study of human papillomavirus (HPV)-induced carcinogenesis uses multiple in vivo mouse models, one of which relies on the cytokeratin 14 gene promoter to drive the expression of all HPV early oncogenes. This study aimed to determine the HPV16 variant and sublineage present in the K14HPV16 mouse model. This information can be considered of great importance to further enhance this K14HPV16 model as an essential research tool and optimize its use for basic and translational studies. Our study evaluated HPV DNA from 17 samples isolated from 4 animals, both wild-type (n = 2) and HPV16-transgenic mice (n = 2). Total DNA was extracted from tissues and the detection of HPV16 was performed using a qPCR multiplex. HPV16-positive samples were subsequently whole-genome sequenced by next-generation sequencing techniques. The phylogenetic positioning clearly shows K14HPV16 samples clustering together in the sub-lineage A1 (NC001526.4). A comparative genome analysis of K14HPV16 samples revealed three mutations to the human papillomaviruses type 16 sublineage A1 representative strain. Knowledge of the HPV 16 variant is fundamental, and these findings will allow the rational use of this animal model to explore the role of the A1 sublineage in HPV-driven cancer.
人乳头瘤病毒（HPV）诱导的致癌作用研究使用了多种体内小鼠模型，其中一种模型依赖细胞角蛋白14基因启动子来驱动所有HPV早期致癌基因的表达。本研究旨在确定K14HPV16小鼠模型中存在的HPV16变体和亚谱系。这些信息对于进一步完善K14HPV16模型作为重要研究工具，并优化其在基础研究和转化研究中的应用具有重要意义。我们的研究评估了从4只动物（野生型，n = 2；HPV16转基因小鼠，n = 2）分离的17个样本中的HPV DNA。从组织中提取总DNA，并使用qPCR多重检测法检测HPV16。随后，通过下一代测序技术对HPV16阳性样本进行全基因组测序。系统发育定位清楚地显示K14HPV16样本聚集在A1亚谱系（NC001526.4）中。对K14HPV16样本的比较基因组分析揭示了16型人乳头瘤病毒A1亚谱系代表性菌株的三个突变。了解HPV 16变体至关重要，这些发现将有助于合理利用该动物模型来探索A1亚谱系在HPV驱动的癌症中的作用。
