MicroRNAs in Viral Infection and Immune Modulation

MicroRNAs (miRNAs) are short non-coding RNA molecules of approximately 22 nucleotides that regulate gene expression through sequence-specific interaction with messenger RNA. In the context of viral infection, host miRNAs can either suppress viral replication by targeting viral genomes or essential host factors, or be co-opted by viruses to evade immune surveillance. Conversely, many viruses encode their own viral miRNAs (v-miRNAs) to manipulate host gene networks, inhibit antiviral pathways and establish persistent infection. The dynamic interplay between host and viral miRNAs orchestrates key aspects of innate and adaptive immunity, including interferon production, pattern-recognition receptor signalling and cytokine cascades. Recent work has revealed that miRNA expression profiles change markedly upon infection with influenza, coronaviruses, flaviviruses and retroviruses, reflecting both host defence strategies and viral countermeasures. Beyond mechanistic insights, miRNAs are emerging as biomarkers of disease severity and as candidates for novel antiviral therapeutics. Delivery of miRNA mimics or inhibitors has been shown to modulate interferon-mediated responses in cell and animal models, opening avenues for targeted intervention. The global significance of miRNA research in infectious disease lies in its potential to inform strategies for vaccination, antiviral drug development and improved diagnostics, thereby reinforcing the central role of small RNAs in immune modulation and viral pathogenesis.

Research from Nature Portfolio

Recent studies have highlighted microRNA-136 as a pivotal dual regulator of innate antiviral immunity. In human lung epithelial cells infected with highly pathogenic influenza A virus, miR-136 was found to bind the 3′ untranslated region of IL-6 mRNA, reducing excessive cytokine expression, while simultaneously acting as an agonist of the retinoic acid-inducible gene I (RIG-I) receptor. This dual activity provokes accumulation of interferon-β and IL-6, thereby reinforcing early antiviral defences. The discovery of miR-136’s capacity to link pattern-recognition receptor activation with fine-tuning of inflammatory mediators underscores the therapeutic promise of harnessing endogenous miRNAs to bolster innate immunity against viral threats.

MicroRNAs in Viral Infection and Immune Modulation publication trend

The graph below shows the total number of articles in micrornas in viral infection and immune modulation across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): A small non-coding RNA of ~22 nucleotides that regulates gene expression by binding complementary sequences in target mRNAs, leading to degradation or translational repression.

Viral microRNA (v-miRNA): A miRNA encoded by a virus that modulates host or viral gene expression to favour viral replication or evade immunity.

Pattern-recognition receptor (PRR): A host sensor, such as RIG-I or Toll-like receptors, that detects conserved pathogen-associated molecular patterns and initiates innate immune responses.

Interferon (IFN): A family of cytokines released by host cells in response to pathogens that activate antiviral gene programmes and modulate immune cell function.

JAK-STAT pathway: A signal transduction cascade triggered by cytokine receptors that leads to activation of signal transducers and activators of transcription, driving expression of interferon-stimulated genes.

Innate immunity: The first line of defence against pathogens, comprising non-specific responses such as phagocytosis, cytokine release and activation of natural killer cells.

References

1. A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection. Medicinal Research Reviews (2024).
2. Therapeutic role of miR-19a/b protection from influenza virus infection in patients with coronary heart disease. Molecular Therapy - Nucleic Acids (2024).
3. miR-191-5p suppresses PRRSV replication by targeting porcine EGFR to enhance interferon signaling. Frontiers in Microbiology (2024).
4. Identification of cellular microRNA-136 as a dual regulator of RIG-I-mediated innate immunity that antagonizes H5N1 IAV replication in A549 cells. Scientific Reports (2015).