Extracellular circulating viral microRNAs: current knowledge and perspectives

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs responsible of post-transcriptional regulation of gene expression through interaction with messenger RNAs (mRNAs). They are involved in important biological processes and are often dysregulated in a variety of diseases, including cancer and infections. Viruses also encode their own sets of miRNAs, which they use to control the expression of either the host's genes and/or their own. In the past few years evidence of the presence of cellular miRNAs in extracellular human body fluids such as serum, plasma, saliva, and urine has accumulated. They have been found either cofractionate with the Argonaute2 protein or in membrane-bound vesicles such as exosomes. Although little is known about the role of circulating miRNAs, it has been demonstrated that miRNAs secreted by virus-infected cells are transferred to and act in uninfected recipient cells. In this work we summarize the current knowledge on viral circulating miRNAs and provide a few examples of computational prediction of their function.

Keywords: body fluids; circulating microRNA; exosomes; microRNA; vesicules; viruses.

FIGURE 1

Summary model of plausible mechanisms for export and functional delivery of viral miRNAs. The image depicts the possible means of transcription, packaging, and functional delivery of viral miRNAs during an infection. Virus-encoded miRNAs are transcribed by the infected cell (A). They could exploit various channels to reach extracellular space and, eventually, be delivered to recipient non-infected cells: inside apoptotic bodies after cell death (B), packaged into exosomes (C), or HDL/LDL molecules or even bound to AGO2 (D). Viral miRNAs may be uptaken by non-infected cells where they could exert their regulatory functions (E).