MicroRNA Functions in Viral Infections and Immune Responses

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and orchestrate host–pathogen interactions during viral infections. Upon viral entry, host-encoded miRNAs can modulate antiviral innate and adaptive immune responses by targeting transcripts involved in interferon production, pattern-recognition receptor signalling and inflammatory mediators. Concurrently, many viruses encode their own miRNAs or manipulate host miRNA pathways to evade immune detection, alter cellular apoptosis and promote replication. Viral miRNA orthologs may mimic host seed sequences to subvert host networks or act as sponges to neutralise antiviral miRNAs. Exosomal miRNAs further facilitate intercellular communication, disseminating immune signals or viral modulators between infected and uninfected cells. The dynamic reciprocity between host and viral miRNAs underpins critical facets of infection outcome, including viral persistence, immunopathology and disease progression. Understanding these mechanisms highlights novel biomarkers for disease diagnosis and therapeutic targets for antiviral intervention, with broad implications for managing respiratory, neurotropic and oncogenic viral diseases globally.

Research from Nature Portfolio

Recent studies have elucidated how host miRNAs can both suppress and enhance viral replication. One investigation revealed that miR-23b is upregulated in avian leukosis virus subgroup J-infected spleens, directly targeting the interferon regulatory factor 1 transcript. Overexpression of miR-23b suppressed IRF1 levels, dampened IFN-β expression and facilitated viral replication, whereas IRF1 restoration impeded viral spread. In another study, miR-16-5p expression increases in cells and neural tissues upon enterovirus 71 infection, driven by virus-induced caspase activation promoting pri-miR-16 processing. MiR-16-5p then forms a positive feedback loop, enhancing apoptosis via caspase-3 activation while concurrently inhibiting viral replication by targeting key cell cycle regulators. These findings underscore the dual roles of host miRNAs in balancing antiviral defence and host cell fate during infection.

MicroRNA Functions in Viral Infections and Immune Responses publication trend

The graph below shows the total number of articles in microrna functions in viral infections and immune responses across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Small non-coding RNA molecule (~22 nucleotides) that binds complementary sequences in target messenger RNAs to repress translation or induce degradation.

Exosome: Nano-sized extracellular vesicle released by cells, containing proteins, lipids and RNAs, including miRNAs, that mediate intercellular communication.

Seed sequence: Nucleotide positions 2–8 at the 5′ end of a miRNA that determine target specificity through base pairing with messenger RNA.

Viral seed mimic (vSM): Viral RNA motif that imitates a host miRNA seed sequence to engage host RNA-silencing machinery and modulate gene expression.

Viral seed sponge (vSS): Viral RNA sequence that binds and sequesters a host miRNA, preventing it from regulating its natural targets.

Interferon regulatory factor 1 (IRF1): Transcription factor that activates genes involved in antiviral interferon responses and immune regulation.

Caspase: Family of cysteine proteases that execute programmed cell death (apoptosis) and can process pri-miRNAs to mature miRNAs under certain conditions.

References

1. MicroRNA-23b Promotes Avian Leukosis Virus Subgroup J (ALV-J) Replication by Targeting IRF1. Scientific Reports (2015).
2. MiR-16-5p mediates a positive feedback loop in EV71-induced apoptosis and suppresses virus replication. Scientific Reports (2017).
3. Exosomal microRNA/miRNA Dysregulation in Respiratory Diseases: From Mycoplasma-Induced Respiratory Disease to COVID-19 and Beyond. Cells (2023).
4. Characterizing Host microRNA: Virus Interactions of Orthoavulavirus javaense. Viruses (2024).