The roles of microRNAs in mammalian virus infection

Abstract

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that are important for the control of a multitude of critical processes in mammalian cells. Increasing evidence supports that miRNAs also have important functions in viral replication and may be used by host cells to control viral infection. Expression of miRNAs has been reported for various groups of viruses including herpesviruses, small DNA viruses and retroviruses. The recent identification of target genes regulated by some of these viral miRNAs suggests that they may function in the control of lytic and latent viral replication, in the limitation of antiviral responses, in the inhibition of apoptosis, and in the stimulation of cellular growth. In this review, we summarize in brief recent findings on the antiviral activities of cellular miRNAs and the viral counter-responses to the cell's RNAi restriction.

Figure 1. Potential functions of viral miRNAs

Like their cellular counterparts, viral miRNAs (red) are produced from hairpin-shaped RNA progenitors and are incorporated into the RNA-induced silencing complex (RISC). Viral miRNAs can act on both, the control of viral genes (top) or on cellular genes (bottom) by repressing their expression. The figure shows examples of miRNAs from different viruses, their targets (blue), and the proposed effects on antiviral immune response, viral replication and persistence, apoptosis and growth control (brown).

Figure 2. Five potential measures used by viruses to counter the cell’s RNAi restriction

A virus particle is shown to infect a cell. In the first “protection” measure, viral RNAs could be sheathed by proteins so as to be protected against access by cellular RNAi. Second, viruses could encode RNA-binding proteins or RNA-decoys that sequester the cell’s RNAi effectors leading to “suppression” of interference. In a third way, viruses can mutate their nucleotide sequences so that previous complementarities present in si-/mi-RNA sequences are not longer valid. The mutations then allow for “evasion” by the viruses from RNAi. Fourth, the virus can change the expression profile of cellular miRNAs producing a “modulation” of miRNA levels. Finally, viruses (red) initially sensitive to restriction by a miRNA could evolve to a form (green) that can beneficially utilize the miRNA for its replication. HCV is a putative example of this “adaptation”.