Pathogens Use and Abuse MicroRNAs to Deceive the Immune System

Emerging evidence has demonstrated that microRNAs (miRs) play a role in the survival and amplification of viruses, bacteria and other pathogens. There are various ways in which pathogens can benefit from miR-directed alterations in protein translation and signal transduction. Members of the herpesviridae family have previously been shown to encode multiple miRs, while the production of miRs by viruses like HIV-1 remained controversial. Recently, novel techniques have facilitated the elucidation of true miR targets by establishing miR-argonaute association and the subsequent interactions with their cognate cellular mRNAs. This, in combination with miR reporter assays, has generated physiologically relevant evidence that miRs from the herpesviridae family have the potential to downregulate multiple cellular targets, which are involved in immune activation, cytokine signaling and apoptosis. In addition, viruses and bacteria have also been linked to the induction of host cellular miRs, which have the capacity to mitigate immune activation, cytokine signaling and apoptosis. Interfering with miR expression may be clinically relevant. In the case of hepatitis C infection, the cellular miR-122 is already targeted therapeutically. This not only exemplifies how important miRs can be for the survival of specific viruses, but it also delineates the potential to use miRs as drug targets. In this paper we will review the latest reports on viruses and bacteria that abuse miR regulation for their benefit, which may be of interest in the development of miR-directed therapies.