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

被引:111
作者
Carnero, Elena [1 ,2 ]
Barriocanal, Marina [1 ,2 ]
Prior, Celia [1 ,2 ]
Pablo Unfried, Juan [1 ,2 ]
Segura, Victor [3 ,4 ]
Guruceaga, Elizabeth [3 ,4 ]
Enguita, Monica [1 ,2 ]
Smerdou, Cristian [1 ,2 ]
Gastaminza, Pablo [5 ]
Fortes, Puri [1 ,2 ]
机构
[1] Univ Navarra, Dept Gene Therapy & Hepatol, Ctr Appl Med Res CIMA, Navarra Inst Hlth Res, Pamplona, Spain
[2] Univ Navarra, Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain
[3] Univ Navarra, Bioinformat Unit, CIMA, Pamplona, Spain
[4] Univ Navarra, IdisNA, Pamplona, Spain
[5] CSIC, Natl Ctr Biotechnol CNB, Madrid, Spain
关键词
EGOT; HCV; lncRNAs; PKR; SFV; HEPATITIS-C VIRUS; INTERFERON-INDUCED PROTEIN; SEMLIKI-FOREST-VIRUS; GENE-EXPRESSION; MESSENGER-RNA; U1; INHIBITION; HUMAN GENOME; HUMAN LIVER; KINASE PKR; IN-VITRO;
D O I
10.15252/embr.201541763
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-kappa B 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.
引用
收藏
页码:1013 / 1028
页数:16
相关论文
共 70 条
[1]   Combination of RNA interference and U1 inhibition leads to increased inhibition of gene expression [J].
Abad, X. ;
Razquin, N. ;
Abad, A. ;
Fortes, P. .
NUCLEIC ACIDS RESEARCH, 2010, 38 (13) :e136-e136
[2]   BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus [J].
Amet, T. ;
Byrd, D. ;
Hu, N. ;
Sun, Q. ;
Li, F. ;
Zhao, Y. ;
Hu, S. ;
Grantham, A. ;
Yu, Q. .
CURRENT MOLECULAR MEDICINE, 2014, 14 (03) :349-360
[3]  
[Anonymous], 2005, BIOINFORMATICS COMPU
[4]   Adenovirus VA RNA-derived miRNAs target cellular genes involved in cell growth, gene expression and DNA repair [J].
Aparicio, Oscar ;
Carnero, Elena ;
Abad, Xabier ;
Razquin, Nerea ;
Guruceaga, Elizabeth ;
Segura, Victor ;
Fortes, Puri .
NUCLEIC ACIDS RESEARCH, 2010, 38 (03) :750-763
[5]   Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response [J].
Arnaud, Noella ;
Dabo, Stephanie ;
Akazawa, Daisuke ;
Fukasawa, Masayoshi ;
Shinkai-Ouchi, Fumiko ;
Hugon, Jacques ;
Wakita, Takaji ;
Meurs, Eliane F. .
PLOS PATHOGENS, 2011, 7 (10)
[6]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[7]   Long non-coding RNA BST2/BISPR is induced by IFN and regulates the expression of the antiviral factor tetherin [J].
Barriocanal, Marina ;
Camero, Elena ;
Segura, Victor ;
Fortes, Puri .
FRONTIERS IN IMMUNOLOGY, 2015, 5 :1-13
[8]   Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation [J].
Bazzini, Ariel A. ;
Johnstone, Timothy G. ;
Christiano, Romain ;
Mackowiak, Sebastian D. ;
Obermayer, Benedikt ;
Fleming, Elizabeth S. ;
Vejnar, Charles E. ;
Lee, Miler T. ;
Rajewsky, Nikolaus ;
Walther, Tobias C. ;
Giraldez, Antonio J. .
EMBO JOURNAL, 2014, 33 (09) :981-993
[9]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[10]   Gene Expression Profiling Indicates the Roles of Host Oxidative Stress, Apoptosis, Lipid Metabolism, and Intracellular Transport Genes in the Replication of Hepatitis C Virus [J].
Blackham, Samantha ;
Baillie, Andrew ;
Al-Hababi, Fadel ;
Remlinger, Katja ;
You, Shihyun ;
Hamatake, Robert ;
McGarvey, Michael J. .
JOURNAL OF VIROLOGY, 2010, 84 (10) :5404-5414