MicroRNA based immunoevasion mechanism of human polyomaviruses

Since miRNAs are considered non-immunogenic, it was not too surprising to discover that some herpesviruses, which are masters of immune evasion, developed their own unique miRNAs to escape immune elimination. In this point of view we discuss our recent findings in which we demonstrate that two polyomaviruses, JC and BK, use an identical miRNA to escape immune attack. This identical miRNA targets the stress-induced protein ULBP3, which is recognized by the killer receptor NKG2D and thus, through the usage of a miRNA, JCV and BKV avoid the NKG2D mediated elimination. We further compare the miRNA-based immune evasion mechanisms of herpes and polyomaviruses, offering new insights on the complexity of the stress induced ligands function and recognition. Lastly, we consider the possibility that other viral and cellular mechanisms are also involved in targeting ULBP3 and other NKG2D ligands.