The Janus face of host LncRNA in viral infections: Defender or collaborator?

Long non-coding RNAs (lncRNAs) are critical context-dependent regulators of viral infection, functioning as double-edged swords in host defense and viral pathogenesis. Accumulating evidence demonstrates that host lncRNAs exert antiviral effects by modulating innate immune responses, regulating host cell survival/apoptosis, or directly targeting viral genomes. Conversely, viruses exploit lncRNA functions to evade immune surveillance, suppress antiviral signaling, and promote viral replication. This review synthesizes current literature to elucidate the molecular mechanisms governing the functional duality of lncRNAs and their dynamic switching between proviral and antiviral roles during infection. Understanding the precise control of this functional switch is crucial for translating lncRNA biology into novel therapeutic strategies. The functional duality of lncRNAs reflects their deep integration into cellular networks. Harnessing their potential demands mechanistic understanding, precision diagnostics, and dynamically responsive interventions. Key lncRNA-pathway interactions offer promising targets for rationally designed RNA-based antivirals against chronic and drug-resistant viruses. A review on long non-coding RNAs as double-edged regulators in viral infection, on the molecular mechanisms of their dynamic antiviral-proviral role switching, and their therapeutic potential for novel RNA-based antivirals.