关键词: HPV integration HPV16 HPV18 cervical cancer nanopore sequencing

来  源:   DOI:10.3389/fmicb.2023.1294146   PDF(Pubmed)

Abstract:
UNASSIGNED: The integration of human papillomavirus (HPV) is closely related to the occurrence of cervical cancer. However, little is known about the complete state of HPV integration into the host genome.
UNASSIGNED: In this study, three HPV-positive cell lines, HeLa, SiHa, and CaSki, were subjected to NANOPORE long-read sequencing to detect HPV integration. Analysis of viral integration patterns using independently developed software (HPV-TSD) yielded multiple complete integration patterns for the three HPV cell lines.
UNASSIGNED: We found distinct differences between the integration patterns of HPV18 and HPV16. Furthermore, the integration characteristics of the viruses were significantly different, even though they all belonged to HPV16 integration. The HPV integration in the CaSki cells was relatively complex. The HPV18 integration status in HeLa cells was the dominant, whereas the percentage of integrated HPV 16 in SiHa and CaSki cells was significantly lower. In addition, the virus sequences in the HeLa cells were incomplete and existed in an integrated state. We also identified a large number of tandem repeats in HPV16 and HPV18 integration. Our study not only clarified the feasibility of high-throughput long-read sequencing in the study of HPV integration, but also explored a variety of HPV integration models, and confirmed that viral integration is an important form of HPV in cell lines.
UNASSIGNED: Elucidating HPV integration patterns will provide critical guidance for developing a detection algorithm for HPV integration, as well as the application of virus integration in clinical practice and drug research and development.
摘要:
人乳头瘤病毒(HPV)的整合与宫颈癌的发生密切相关。然而,关于HPV整合到宿主基因组中的完整状态知之甚少。
在这项研究中,三种HPV阳性细胞系,HeLa,SiHa,还有CaSki,进行NANOPERE长读数测序以检测HPV整合。使用独立开发的软件(HPV-TSD)对病毒整合模式的分析产生了三种HPV细胞系的多个完整整合模式。
我们发现HPV18和HPV16的整合模式之间存在明显差异。此外,病毒的整合特征明显不同,尽管它们都属于HPV16集成。CaSki细胞中的HPV整合相对复杂。HPV18在HeLa细胞中的整合状态占优势,而SiHa和CaSki细胞中整合的HPV16的百分比显着降低。此外,HeLa细胞中的病毒序列是不完整的,并以整合状态存在。我们还在HPV16和HPV18整合中鉴定了大量的串联重复序列。本研究不仅阐明了高通量长序列测序在HPV整合研究中的可行性,还探索了多种HPV整合模型,并证实病毒整合是HPV在细胞系中的重要形式。
阐明HPV整合模式将为开发HPV整合检测算法提供关键指导,以及病毒整合在临床实践和药物研发中的应用。
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