Long noncoding RNA EGOT negatively affects the antiviral response and favors HCV replication.
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-κB 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.
Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA) and IdiSNA Navarra Institute for Health Research University of Navarra, Pamplona, Spain.
Elena
E
Carnero
Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA) and IdiSNA Navarra Institute for Health Research University of Navarra, Pamplona, Spain.
Marina
M
Barriocanal
Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA) and IdiSNA Navarra Institute for Health Research University of Navarra, Pamplona, Spain.
Celia
C
Prior
Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA) and IdiSNA Navarra Institute for Health Research University of Navarra, Pamplona, Spain.
Juan
J
Pablo Unfried
Bioinformatics Unit, CIMA and IdisNA University of Navarra, Pamplona, Spain.
Victor
V
Segura
Bioinformatics Unit, CIMA and IdisNA University of Navarra, Pamplona, Spain.
Elizabeth
E
Guruceaga
Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA) and IdiSNA Navarra Institute for Health Research University of Navarra, Pamplona, Spain.
Mónica
M
Enguita
Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA) and IdiSNA Navarra Institute for Health Research University of Navarra, Pamplona, Spain.
Cristian
C
Smerdou
National Center of Biotechnology CNB/CSIC, Madrid, Spain.
Pablo
P
Gastaminza
Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA) and IdiSNA Navarra Institute for Health Research University of Navarra, Pamplona, Spain pfortes@unav.es.
Puri
0000-0001-7571-6220
P
Fortes
D045744:Cell Line, Tumor; D016000:Cluster Analysis; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D060467:Disease Resistance / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D042541:Intracellular Space; D016366:Open Reading Frames; D034443:RNA Transport; D062085:RNA, Long Noncoding / Q000235:genetics*; D051193:Toll-Like Receptors / Q000378:metabolism; D059467:Transcriptome; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000378:metabolism
C000606999:EGOT lncRNA, human; D062085:RNA, Long Noncoding; D051193:Toll-Like Receptors; D007371:Interferon-gamma; C000602769:EIF2AK2 protein, human; D019892:eIF-2 Kinase; D000071457:DEAD Box Protein 58
EGOT; HCV; PKR; SFV; lncRNAs