Innate Immune Response Mechanisms in Viral Infections

The innate immune system constitutes the first line of defence against viral pathogens, relying on germline-encoded receptors to detect conserved viral signatures. Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) on cell surfaces and endosomes, RIG-I-like receptors (RLRs) within the cytosol, nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) and cytosolic DNA sensors, recognise viral nucleic acids or proteins. Engagement of these receptors triggers adaptor proteins such as MAVS, MyD88 and TRIF, leading to the activation of transcription factors NF-κB and interferon regulatory factors (IRFs). IRF-mediated transcription initiates production of type I and type III interferons (IFNs), which signal through distinct receptors to induce interferon-stimulated genes (ISGs) that constrain viral replication and modulate the inflammatory milieu. Post-translational modifications, notably phosphorylation and ubiquitination of sensors and adaptors, fine-tune signal propagation, while negative regulators prevent excessive tissue damage. Viruses counteract these mechanisms through evasion strategies targeting PRRs and signal transducers. Understanding the interplay between receptor activation, IFN amplification loops and regulatory feedback has yielded insights into antiviral therapeutics, immunomodulation in chronic infection and cancer immunotherapy strategies.

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Innate Immune Response Mechanisms in Viral Infections publication trend

The graph below shows the total number of articles in innate immune response mechanisms in viral infections across all publications each year (not limited to Nature Index journals).

Technical terms

Pattern recognition receptor (PRR): A germline-encoded sensor that detects conserved microbial or viral motifs to trigger innate immune signalling.

RIG-I-like receptor (RLR): A family of cytosolic RNA sensors, including RIG-I, MDA5 and LGP2, that recognise viral RNA and activate antiviral pathways.

Interferon regulatory factor (IRF): A transcription factor family central to the induction of interferons and interferon-stimulated genes during viral infection.

Interferon (IFN): A cytokine produced in response to viral sensing that binds to specific receptors to induce antiviral gene expression.

Interferon-stimulated gene (ISG): A gene whose transcription is upregulated by interferon signalling, encoding proteins that inhibit viral replication or modulate immunity.

References

1. The multiple roles of interferon regulatory factor family in health and disease. Signal Transduction and Targeted Therapy (2024).
2. Exploiting RIG-I-like receptor pathway for cancer immunotherapy. Journal of Hematology & Oncology (2023).
3. Pattern Recognition Receptors and the Innate Immune Response to Viral Infection. Viruses (2011).
4. Intracellular sensing of viral genomes and viral evasion. Experimental & Molecular Medicine (2019).
5. Type I and Type III Interferons Drive Redundant Amplification Loops to Induce a Transcriptional Signature in Influenza-Infected Airway Epithelia. PLOS Pathogens (2013).