病毒诱导的APOBEC3转变发生在膀癌开始时
George H Hatton1, Sally R James2, Andrew S Mason1
1Jack Birch Unit for Molecular Carcinogenesis, Department of Biology and York Biomedical Research Institute, University of York, Heslington, York, UK.
Science advances
|December 3, 2025
概括
乙基多瘤病毒 (BKPyV) 感染触发了尿路细胞中的APOBEC3酶活性,导致导致导致膀癌的突变. 这种"转基因变异"表明尿路细胞癌可能可以通过抗病毒疗法预防.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 遗传学 遗传学 是一个
背景情况:
- 人类尿中的致癌包括来自APOBEC3酶的高突变负担,但病毒原因尚未确立.
- 乙基多瘤病毒 (BKPyV) 是一种常见的病毒,在脏中持续存在,在尿液中检测到,可能与泌尿器变化有关.
研究的目的:
- 研究BKPyV感染在诱导APOBEC3表达和随后的尿路细胞癌发生中的作用.
- 探索"转变异性"的机制,即旁观者细胞因附近的病毒感染而获得突变.
主要方法:
- 在正常人尿膜模型中诱导慢性BKPyV感染.
- 对先天免疫反应的分析,包括细胞挤出和干扰素信号传递.
- 在受感染和旁观者细胞中评估APOBEC3表达和突变特征.
主要成果:
- BKPyV感染诱导了细胞挤出和膜干扰素信号传递的先天反应,增加了APOBEC3的表达.
- 感染细胞和旁观者细胞中的APOBEC3活性产生了突变特征,反映了肌肉侵入性膀癌中的突变特征.
- 在BKPyV感染附近的未感染的旁观者细胞获得了APOBEC3驱动的突变,获得了超变的优势.
结论:
- BKPyV感染可以通过诱导APOBEC3介导的突变在受感染和旁观者细胞通过"转基因变异".
- 这种机制解释了病毒阴性,富含APOBEC3的尿路细胞癌,这表明通过抗病毒干预可以预防.
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