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.

Department of Immunobiology Yale School of Medicine New Haven CT 06520 8011 USA

Institute of Biomedicine University of Turku Turku 20520 Finland

Institute of Biomedicine University of Turku Turku 20520 Finland; Turku Doctoral Programme of Molecular Medicine University of Turku Turku Finland

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague 14220 Czech Republic

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bioRxiv. 2024 Jan 09:2024.01.09.574829. doi: 10.1101/2024.01.09.574829. PubMed

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