Merkel cell polyomavirus, a highly prevalent virus with tumorigenic potential

•We summarize current knowledge on the MCPyV life cycle and transformation.•We discuss properties of MCPyV contributing to tumorigenesis in its natural host.•We describe putative mechanisms of MCPyV replication and persistence.

Merkel cell polyomavirus (MCPyV) is the only human polyomavirus known to be involved in tumorigenesis. Like other human polyomaviruses, MCPyV is highly prevalent in the healthy population, yet the MCPyV-associated Merkel cell carcinoma (MCC) is a very rare disease. Although in vitro and in vivo models have provided significant details regarding molecular functions of viral oncoproteins during cellular transformation, many open questions about the natural life cycle of the virus, its mechanisms of persistence and the precise role of MCPyV during MCC pathogenesis remain. This review will carve out the specifics of MCPyV biology and discuss unresolved issues to help the reader gain a better understanding of what may differentiate MCPyV from other polyomaviruses.