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The SV40 virus enhancer functions as a somatic hypermutation-targeting element with potential tumorigenic activity
Tekijät: Šenigl, Filip; Soikkeli, Anni I.; Prost, Salomé; Schatz, David G.; Slavková, Martina; Hejnar, Jiří; Alinikula, Jukka
Kustantaja: Elsevier BV
Julkaisuvuosi: 2024
Journal: Tumour Virus Research
Tietokannassa oleva lehden nimi: Tumour virus research
Lehden akronyymi: Tumour Virus Res
Artikkelin numero: 200293
Vuosikerta: 18
eISSN: 2666-6790
DOI: https://doi.org/10.1016/j.tvr.2024.200293
Verkko-osoite: https://doi.org/10.1016/j.tvr.2024.200293
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/459169034
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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This work was supported by the Czech Science Foundation (project 22-30384S to F.Š.); Czech Academy of Sciences (Premium Academiae Award 2018 to J.H.); the Finnish Cultural Foundation (to J.A.); the Sigrid Juselius Foundation (to J.A.), the Turku University Foundation (to J.A.); the Finnish Cultural Foundation Kymenlaakso Regional Fund (to A.S.); the Alfred Kordelin Foundation (to A.S.); and Cancer Society of Southwest Finland (to A.S. and J.A.); and National Institutes of Health (R01 AI 127642 to D.G.S.). FŠ and J.H. were supported by the project National Institute of Virology and Bacteriology (program EXCELES, no. LX22NPO5103) funded by the European Union–Next Generation EU; we also acknowledge institutional support from the project RVO (68378050).
