SV40 病毒增强子是一种具有潜在致瘤活性的体细胞突变靶向元件

IF 4.7 Q1 VIROLOGY
Filip Šenigl , Anni I. Soikkeli , Salomé Prost , David G. Schatz , Martina Slavková , Jiří Hejnar , Jukka Alinikula
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引用次数: 0

摘要

猿猴病毒 40(SV40)是一种猴病毒,在啮齿类动物中具有致瘤潜能,与包括淋巴瘤在内的几种人类癌症有关。一种相关的梅克尔细胞多瘤病毒通过表达截短的大肿瘤抗原(LT)导致人类患癌,截短抗原是由 APOBEC 家族的胞苷脱氨酶诱导突变引起的。AID(活化诱导胞苷脱氨酶)是 APOBEC 家族的成员之一,是抗体多样化过程(即体细胞高突变)的启动器,其异常表达和靶向是淋巴瘤发生的一个常见来源。在这项研究中,我们研究了 AID 是否会导致 SV40 LT 发生突变。我们证明,SV40增强子在几种细胞类型中具有很强的体细胞超突变靶向活性,AID诱导的突变在B细胞和肾细胞的SV40 LT中积累,并导致B细胞中LT表达截短。我们的研究结果表明,SV40增强子靶向LT的体细胞超突变能力是LT截短事件的潜在来源,而LT截短事件可能会导致各种细胞类型的肿瘤发生,从而通过一种新的突变途径将SV40感染与恶性发展联系起来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The SV40 virus enhancer functions as a somatic hypermutation-targeting element with potential tumorigenic activity
Simian virus 40 (SV40) is a monkey virus with tumorigenic potential in rodents and is associated with several types of human cancers, including lymphomas. A related Merkel cell polyomavirus causes carcinoma in humans by expressing truncated large tumor antigen (LT), with truncations caused by APOBEC family of cytidine deaminase-induced mutations. AID (activation-induced cytidine deaminase), a member of the APOBEC family, is the initiator of the antibody diversification process known as somatic hypermutation and its aberrant expression and targeting is a frequent source of lymphomagenesis. In this study, we investigated whether AID could cause mutations in SV40 LT. We demonstrate that the SV40 enhancer has strong somatic hypermutation targeting activity in several cell types and that AID-induced mutations accumulate in SV40 LT in B cells and kidney cells and cause truncated LT expression in B cells. Our results argue that the ability of the SV40 enhancer to target somatic hypermutation to LT is a potential source of LT truncation events that could contribute to tumorigenesis in various cell types, thereby linking SV40 infection with malignant development through a novel mutagenic pathway.
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来源期刊
Tumour Virus Research
Tumour Virus Research Medicine-Infectious Diseases
CiteScore
6.50
自引率
2.30%
发文量
16
审稿时长
56 days
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