Polyomavirus miRNAs: the beginning

•Polyomaviruses encode a single miRNA.•The miRNA regulates expression of the major viral regulatory protein, large T antigen.•The viral miRNA restricts viral replication.

Polyomaviruses are small, double stranded DNA viruses that replicate in the nucleus of the infected cell. Since 2005, clear evidence for miRNAs has been presented for a subset of the members of this viral family, each of which express a single miRNA. All the miRNAs share in common the ability to regulate expression of the major viral regulatory protein, large T antigen. Growing evidence suggests that the major role of the miRNA is to control viral replication. In vitro studies suggesting an immmunomodulatory role for the miRNA have not been supported by in vivo infections. Very little is known about cellular targets of the viral miRNAs, however. Thus, much remains to be learned about these interesting non-coding RNAs.