Mechanisms and Research Progress of LncRNA-Mediated Regulation of Viral Infections

Long non-coding RNAs (lncRNAs), a class of RNA molecules whose transcripts exceed 200 nucleotides in length and typically lack protein-coding capacity, were once widely regarded as “transcriptional noise.” However, recent studies have shown that lncRNAs can encode small peptides and play critical roles in biological processes, including gene expression regulation, cell differentiation, and immune response. Viral infections, as a common disease, can reshape the transcriptome of host cells, in which the differential expression of lncRNAs is a core link in host–virus interactions. This review aims to deeply analyze the multidimensional regulatory mechanisms of lncRNAs in the host antiviral innate immune response. It elaborates in detail on how lncRNAs construct the host antiviral defense by regulating pattern recognition receptor (PRR) signaling pathways, the production and signal transduction of interferons (IFNs), as well as the expression of interferon-stimulated genes (ISGs). Additionally, we conducted an in-depth analysis of the complex functions of lncRNAs in regulating programmed cell death (PCD), including key processes such as pyroptosis, autophagy, and apoptosis, and integrated specific research cases in infections caused by multiple significant viruses, including influenza A virus (IAV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aim to provide novel strategies for the diagnosis, treatment, and prevention of viral diseases.