Identification of a polyomavirus microRNA highly expressed in tumors

•MCPyV and related viruses (PtvPyV2a, GggPyV1, RacPyV) encode a miRNA in similar genomic positions•These miRNAs can negatively regulate reporters of early viral gene expression•Unlike MCPyV positive tumors, RacPyV miRNA is abundant in RacPyV-associated tumors•The RacPyV miRNA is the first polyomaviral miRNA shown to be abundant in tumors

Polyomaviruses (PyVs) are associated with tumors including Merkel cell carcinoma (MCC). Several PyVs encode microRNAs (miRNAs) but to date no abundant PyV miRNAs have been reported in tumors. To better understand the function of the Merkel cell PyV (MCPyV) miRNA, we examined phylogenetically-related viruses for miRNA expression. We show that two primate PyVs and the more distantly-related raccoon PyV (RacPyV) encode miRNAs that share genomic position and partial sequence identity with MCPyV miRNAs. Unlike MCPyV miRNA in MCC, RacPyV miRNA is highly abundant in raccoon tumors. RacPyV miRNA negatively regulates reporters of early viral (T antigen) transcripts, yet robust viral miRNA expression is tolerated in tumors. We also identify raccoon miRNAs expressed in RacPyV-associated neuroglial brain tumors, including several likely oncogenic miRNAs (oncomiRs). This work describes the first PyV miRNA abundantly expressed in tumors and is consistent with a possible role for both host and viral miRNAs in RacPyV-associated tumors.