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

SIMPLE SUMMARY: Viral outbreaks continue to be an obstacle to human health, with the Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV-2) pandemic shedding light on the current vulnerabilities of our healthcare system. Understanding viral pathology is paramount in developing methods to combat infection. The study of microRNAs (miRNAs) is relatively new to the world of virology research. These small strands of nucleotides are a versatile tool in the regulation of gene expression. Various miRNAs have roles in immune development, immune and inflammatory responses, and viral infections. Changes in miRNA expression can be a double-edged sword, used to alter cell activities to help the host fight infections or taken advantage of by viruses to enhance infection. Uncovering these interactions and their implications can provide direction for therapeutic and diagnostic advancement. Further, miRNAs may have the potential to predict the severity of viral infection and possible health outcomes, as well as track disease progression to inform treatment options. miRNA technology is also anticipated to be highly marketable and has already entered the realm of commercial biopharmaceuticals. Continuing to elucidate the functions of miRNA during infection and the therapeutic potential of these molecules will contribute to new strategies in the battle against current and future 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.