Long noncoding RNA EGOT negatively affects the antiviral response and favors HCV replication

Abstract

The role of long noncoding RNAs (lncRNAs) in viral infection is poorly studied. We have identified hepatitis C virus (HCV)-Stimulated lncRNAs (CSRs) by transcriptome analysis. Interestingly, two of these CSRs (PVT1 and UCA1) play relevant roles in tumorigenesis, providing a novel link between HCV infection and development of liver tumors. Expression of some CSRs seems induced directly by HCV, while others are upregulated by the antiviral response against the virus. In fact, activation of pathogen sensors induces the expression of CSR32/EGOT. RIG-I and the RNA-activated kinase PKR sense HCV RNA, activate NF-jB and upregulate EGOT. EGOT is increased in the liver of patients infected with HCV and after infection with influenza or Semliki Forest virus (SFV). Genome-wide guilt-by-association studies predict that EGOT may function as a negative regulator of the antiviral pathway. Accordingly, EGOT depletion increases the expression of several interferon-stimulated genes and leads to decreased replication of HCV and SFV. Our results suggest that EGOT is a lncRNA induced after infection that increases viral replication by antagonizing the antiviral response.

A Long Noncoding RNA Regulates Hepatitis C Virus Infection Through Interferon Alpha–Inducible Protein 6

“…lncRNAs have been reported to play important roles in the regulation of the IFN response and ISG induction in HCV infection . For example, the lncRNA EGOT has been shown to increase HCV replication by suppressing the antiviral response through the NF‐κB pathway . HCV infection in turn activates PKR and induces NF‐κB, EGOT, and, subsequently, ISG15 transcription to block the RIG‐I pathway, inhibiting the expression of several ISGs to enhance HCV replication .…”

Long noncoding RNA eosinophil granule ontogeny transcript inhibits cell proliferation and migration and promotes cell apoptosis in human glioma

“…Notably, the functional roles of EGOT have recently been implicated in ischemic heart diseases (23). Furthermore, another study has found that lncRNA EGOT negatively affects the antiviral response and favors hepatic virus C (HCV) replication (24). These pioneering studies have suggested that EGOT may exert active functional roles in human diseases, including human cancer.…”

“…Instead, the intrinsic pathway may be involved in the apoptosis induction processes induced by EGOT overexpression. However, as a recent report indicated that lncRNA EGOT prefers nuclear localization in HCV-infected cells (24), the subcellular localization of EGOT in human tumor cells remains to be elucidated and merits further investigation into whether the subcellular location is associated with its regulation of cell apoptosis.…”

Preliminary investigation of five novel long non-coding RNAs in hepatocellular carcinoma cell lines

“…Numerous studies have suggested that some lncRNAs could affect virus infection and replication. For example, EGOT affects the antiviral response to HCV, lncRHOXF1 promotes replication of the Sendai virus, and NEAT1 is related to infection with the influenza virus (16)(17)(18). Thus, significant components of HCC treatment are steps to counter the tumor and viruses.…”