MicroRNAs: Small but Key Players in Viral Infections and Immune Responses to Viral Pathogens

Abstract

Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine.

Keywords: miRNA; miRNA diagnostics; miRNA therapeutics; microRNA; viral infection.

Figure 1

Summary of miRNA regulated processes in immunity.

Figure 2

Biogenesis of miRNA during viral infection and possible effects. miRNA may be encoded by the host or virus. Viruses may upregulate or downregulate endogenous miRNA. miRNA may bind the viral genome, mRNA, or be packaged in an exosome for export to other cells. The binding site of miRNA at the 3′ or 5′ UTR of its mRNA target may alter stability of mRNA or inhibit translation.

Figure 3

Antiviral miRNAs inhibit viral replication (left) including (a) viral entry, (b) transcription of the viral genome, (c) viral protein production, (d) viral assembly, and (e) viral escape. Antiviral miRNAs enhance antiviral cellular processes (right) including (f) cell signaling pathways (g) transcription of ISGs, (h) antiviral cellular protein production, (i) interferon release, and (j) immune cell recognition. Pro-viral miRNAs have opposing effects.