The SV40 virus enhancer functions as a somatic hypermutation-targeting element with potential oncogenic activity

Area of Science:

• Virology
• Oncology
• Molecular Biology

Background:

• Simian virus 40 (SV40) is linked to human cancers like mesothelioma and lymphoma, but its oncogenic mechanism remains unclear.
• Merkel cell polyomavirus (MCPyV), a relative of SV40, causes Merkel cell carcinoma by expressing truncated large tumor antigen (LT) via APOBEC enzyme mutations.
• Activation-induced cytidine deaminase (AID) is an APOBEC family member crucial for antibody diversification via somatic hypermutation (SHM) and implicated in lymphomagenesis.

Approach:

• Investigated if AID-induced mutations could truncate SV40 LT.
• Assessed the SV40 enhancer's activity in targeting SHM across different cell types.
• Examined AID-induced mutations in SV40 LT within B cells and kidney cells.

Key Points:

• The SV40 enhancer exhibits significant SHM targeting activity in multiple cell types.
• AID-induced mutations were observed to accumulate in SV40 LT.
• Truncated SV40 LT expression was detected in B cells due to AID activity.

Conclusions:

• The SV40 enhancer's ability to direct SHM towards LT is a potential mechanism for LT truncation.
• This LT truncation, driven by AID, may contribute to the development of SV40-associated cancers in various human tissues.