Widespread evidence of viral miRNAs targeting host pathways

Abstract

Background: MicroRNAs (miRNA) are regulatory genes that target and repress other RNA molecules via sequence-specific binding. Several biological processes are regulated across many organisms by evolutionarily conserved miRNAs. Plants and invertebrates employ their miRNA in defense against viruses by targeting and degrading viral products. Viruses also encode miRNAs and there is evidence to suggest that virus-encoded miRNAs target specific host genes and pathways that may be beneficial for their infectivity and/or proliferation. However, it is not clear whether there are general patterns underlying cellular targets of viral miRNAs.

Results: Here we show that for several of the 135 known viral miRNAs in human viruses, the human genes targeted by the viral miRNA are enriched for specific host pathways whose targeting is likely beneficial to the virus. Given that viral miRNAs continue to be discovered as technologies evolve, we extended the investigation to 6809 putative miRNAs encoded by 23 human viruses. Our analysis further suggests that human viruses have evolved their miRNA repertoire to target specific human pathways, such as cell growth, axon guidance, and cell differentiation. Interestingly, many of the same pathways are also targeted in mice by miRNAs encoded by murine viruses. Furthermore, Human Cytomegalovirus (CMV) miRNAs that target specific human pathways exhibit increased conservation across CMV strains.

Conclusions: Overall, our results suggest that viruses may have evolved their miRNA repertoire to target specific host pathways as a means for their survival.

Figure 1

Possible interactions between miRNA and target genes. (a) Endogenous host miRNAs target specific host genes. (b) Host miRNAs target viral genes. (c) Virus encoded miRNAs target viral genes to mediate immune evasion or maintenance of latency. (d) Viral miRNAs have been shown to target specific host genes.