Merkel cell polyomavirus small tumor antigen contributes to immune evasion by interfering with type I interferon signaling [RNA-Seq]
Merkel cell polyomavirus (MCPyV) is linked to Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. This study investigated the influence of MCPyV T antigens on the host genome using transcriptomics and epigenomics. Results revealed a role for the small Tumor (sT) antigen in subverting type I interferon response and immune evasion, contributing to persistent infection and tumor progression. These findings enhance our understanding of MCPyV pathogenesis and may inform new therapeutic strategies. Overall design: Use of a lentiviral transduction system to overexpress MCPyV T antigens (large Tumor (LT), small Tumor (sT), and truncated LT (LTtr)) in primary human dermal fibroblasts. Transcriptional profiling to investigate the interaction of T antigens with host cellular gene regulatory processes, focusing on inflammatory cytokines and interferon-stimulated genes (ISGs). Analysis of transcriptional changes induced by T antigens, such as the induction of inflammatory cytokines by both sT and LT, the short-term induction of ISGs by LT, and the stable repression of ISG transcription by sT. Investigation of the balancing effect of sT on immune recognition during the initial phase of infection and its potential role in maintaining a persistent infection. Evaluation of the transcriptional changes when sT is co-overexpressed with LTtr, reflecting the immunogenic feature of MCCs and their ability to attract innate and adaptive immune cells.