Comparative innate immune responses across major RNA and DNA viral infections: Mechanisms, immunopathology, and therapeutic perspectives

Innate immunity is the first defense against viral infections, limiting viral replication and initiating adaptive immunity. Viral pathogens are recognized by pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), (RIG-I-like receptors) RLRs, and the (cyclic GMP-AMP synthase) cGAS-STING pathway, which trigger interferon production and antiviral responses. This review compares innate immune responses to major RNA viruses (influenza, SARS-CoV-2, HIV) and DNA viruses (HSV, HBV, CMV). While these viruses activate similar pathways, they differ in interferon dynamics, inflammatory responses, immune cell activation, and immune evasion mechanisms. RNA viruses often induce rapid and strong innate responses, whereas many DNA viruses establish persistence through immune modulation. Dysregulated innate immunity can contribute to cytokine storms, chronic inflammation, and tissue damage. Therapeutic strategies targeting innate immunity, such as interferons, cytokine inhibitors, PRR agonists, and host-directed antivirals, may improve outcomes. Infection severity depends on the timing, magnitude, and regulation of innate immune responses.