LncRNAs in HCV Infection and HCV-Related Liver Disease

Abstract

Long non-coding RNAs (lncRNAs) are transcripts with poor coding capacity that may interact with proteins, DNA, or other RNAs to perform structural and regulatory functions. The lncRNA transcriptome changes significantly in most diseases, including cancer and viral infections. In this review, we summarize the functional implications of lncRNA-deregulation after infection with hepatitis C virus (HCV). HCV leads to chronic infection in many patients that may progress to liver cirrhosis and hepatocellular carcinoma (HCC). Most lncRNAs deregulated in infected cells that have been described function to potentiate or block the antiviral response and, therefore, they have a great impact on HCV viral replication. In addition, several lncRNAs upregulated by the infection contribute to viral release. Finally, many lncRNAs have been described as deregulated in HCV-related HCC that function to enhance cell survival, proliferation, and tumor progression by different mechanisms. Interestingly, some HCV-related HCC lncRNAs can be detected in bodily fluids, and there is great hope that they could be used as biomarkers to predict cancer initiation, progression, tumor burden, response to treatment, resistance to therapy, or tumor recurrence. Finally, there is high confidence that lncRNAs could also be used to improve the suboptimal long-term outcomes of current HCC treatment options.

LncRNAs in the Type I Interferon Antiviral Response

“…Several viruses express viral lncRNAs that play critical regulatory functions in the infected cell [ 100 , 101 ]. Also, human and mouse viruses promote profound changes in the expression of cellular lncRNAs [ 102 , 103 , 104 , 105 ]. Interestingly, different viruses deregulate the same host lncRNAs in infected cells as a consequence of the activation of the antiviral response [ 102 , 104 , 106 ].…”

“…Also, human and mouse viruses promote profound changes in the expression of cellular lncRNAs [ 102 , 103 , 104 , 105 ]. Interestingly, different viruses deregulate the same host lncRNAs in infected cells as a consequence of the activation of the antiviral response [ 102 , 104 , 106 ]. Out of the myriad of viral-induced lncRNAs described to date, only a handful have been thoroughly studied at the molecular level.…”

“…Transcriptomic analysis comparing IFN-α-treated and control cells show a massive deregulation of the coding and non-coding genome [ 102 , 118 ]. Interestingly, many lncRNAs upregulated after IFN-α treatment, are located near (convergent, divergent, or in tandem) to coding ISGs or inflammatory genes.…”

“…AK006025 associates with CREB-binding Protein/p300 (CBP/p300), contributes to the increased acetylation in the promoter of CXCL9, 10, and 11 genes, and causes the increased expression of these genes. EGOT is a lncRNA highly induced by infection with RNA viruses or RNA mimics and by the activation of different stress-response pathways, including NF-κB and PI3K/AKT [ 102 , 182 ]. Under conditions of HCV infection, EGOT further inhibits the low levels of several ISGs contributing to HCV replication [ 102 ].…”

Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication

“…The resulting liver-derived mixed lipo-viro particles serve to hide the virus from the immune system and to enhance uptake of the viral particles by the next hepatocyte host cell by the use of apolipoproteins [ 6 , 10 , 13 ]. Moreover, HCV has developed several strategies to counteract the immune response [ 14 , 15 , 16 ], including the use of cellular long non-coding RNAs [ 17 , 18 ]. Chronic HCV infection is often recognized only accidentally, e.g., during hospitalization, a reason why virus spread in the population is often unnoticed [ 14 , 15 ].…”