Long Non-Coding RNAs in Viral Immunity: From Regulatory Mechanisms to Therapeutic Potential

Long non-coding RNAs (lncRNAs) are a class of regulatory RNAs that do not encode proteins but play essential roles in controlling gene expression at multiple levels, including chromatin modification, transcription, and RNA stability. LncRNAs have emerged as important regulators of antiviral immunity. These molecules function in both cis and trans to modulate chromatin states, guide transcription factors, scaffold signaling complexes, or act as decoys for regulatory proteins and RNAs. During viral infection, host lncRNAs are dynamically expressed and can either enhance antiviral responses or be hijacked by viruses to suppress immunity, promote replication, or facilitate latency. Virus-encoded lncRNAs also manipulate host gene expression to their advantage. Recent research has uncovered specific lncRNAs involved in regulating interferon signaling, cytokine production, antigen presentation, and immune cell differentiation. Concurrently, advances in computational biology have enabled the discovery and characterization of lncRNAs through methods such as RNA-seq analysis, transcript assembly, coding potential prediction, co-expression network analysis, and interaction modeling with proteins and RNAs. Functional inference is further supported by enrichment analyses and studies of conservation and localization. This mini review summarizes the current understanding of host and viral lncRNAs in antiviral defense and pathogenesis. It also highlights the translational potential of lncRNAs as biomarkers and therapeutic targets, discussing emerging strategies including CRISPR-based modulation, synthetic RNA therapeutics, and innovative delivery methods. Together, these findings underscore the critical role of lncRNAs in viral immunity and their promise in guiding novel approaches for diagnosing and treating viral infections.