Aid or Antagonize: Nuclear Long Noncoding RNAs Regulate Host Responses and Outcomes of Viral Infections

Abstract

Long noncoding RNAs (lncRNAs) are transcripts measuring >200 bp in length and devoid of protein-coding potential. LncRNAs exceed the number of protein-coding mRNAs and regulate cellular, developmental, and immune pathways through diverse molecular mechanisms. In recent years, lncRNAs have emerged as epigenetic regulators with prominent roles in health and disease. Many lncRNAs, either host or virus-encoded, have been implicated in critical cellular defense processes, such as cytokine and antiviral gene expression, the regulation of cell signaling pathways, and the activation of transcription factors. In addition, cellular and viral lncRNAs regulate virus gene expression. Viral infections and associated immune responses alter the expression of host lncRNAs regulating immune responses, host metabolism, and viral replication. The influence of lncRNAs on the pathogenesis and outcomes of viral infections is being widely explored because virus-induced lncRNAs can serve as diagnostic and therapeutic targets. Future studies should focus on thoroughly characterizing lncRNA expressions in virus-infected primary cells, investigating their role in disease prognosis, and developing biologically relevant animal or organoid models to determine their suitability for specific therapeutic targeting. Many cellular and viral lncRNAs localize in the nucleus and epigenetically modulate viral transcription, latency, and host responses to infection. In this review, we provide an overview of the role of nuclear lncRNAs in the pathogenesis and outcomes of viral infections, such as the Influenza A virus, Sendai Virus, Respiratory Syncytial Virus, Hepatitis C virus, Human Immunodeficiency Virus, and Herpes Simplex Virus. We also address significant advances and barriers in characterizing lncRNA function and explore the potential of lncRNAs as therapeutic targets.

Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses

“…Long ncRNAs (lncRNAs) constitute nearly 68% of the transcriptome and were suggested to have a significant regulatory role in antiviral interferon (IFN) response, viral transcription, and latency [99]. Analysis of a selected panel of very long ncR-NAs (>5 kb) in PBMCs could differentiate ME/CFS from healthy donors and relate to altered responses to oxidative stress, chronic viral infection, and hypoxemia [100].…”

“…EBV-induced lncRNAs can modulate viral gene transcription and host gene expression by modifying histone marks at gene promoters. They may affect cellular processes such as the IFN responses, the unfolded protein response, and mitochondrial antiviral signaling [99]. EBV can generate circR-NAs, including spliced transcripts in the BART region [125] and have been found in clinical samples from EBV-related cancers [126].…”

A Synopsis of Hepatitis C Virus Treatments and Future Perspectives

“…The miRNAs can also be considered key players in the antiviral response. New reports on miRNA have provided insights into single and multiple infections and possible targets for therapy [116,117,152,153]. However, large-scale studies are required to validate the miRNA signatures in HCV-infected and coinfected individuals and their response to treatment.…”

Lnc-RPS6P3 Inhibits Influenza A Virus Replication and Attenuates the Inhibitory Effect of NS1 on Innate Immune Response

“…MxA can effectively block highly pathogenic influenza A virus replication [22,23]. Currently, more and more studies are reporting that non-coding RNAs (lncRNA, circ-RNA) affect IAV replication in both positive and negative manners [24]. LncRNA-155 suppresses IAV replication by activating host antiviral innate immunity [25].…”