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Series GSE15323 Query DataSets for GSE15323
Status Public on Jan 03, 2011
Title The differentially expressed genes induced by EV71 infection
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Virus infection may shut off host protein synthesis in order to achieve the replicative advantage over host cells. It is well known that human pathogenic viruses, particularly the picornaviruses, can block host protein synthesis by cleavage or inhibition of eukaryotic initiation factors (eIFs). In this study we found a novel mechanism that microRNA (miRNA) is involved in viral pathogenesis. Infection of enteroviruses can disturb the expression of host miRNAs, in which miR-141 is up-regulated and inhibits host protein synthesis by post-transcriptional repression of the target gene eIF4E, a key element for cap-dependent translation of host proteins. Knockdown of miR-141 by a specific siRNA, antagomiR-141, could restore host eIF4E expression, delay the occurrence of cytopathic effect (CPE), and impair virus propagation. We demonstrated that EV71 infection could increase early growth response 1 (EGR1) expression which induced miR-141 causing the eIF4E suppression; while silencing of EGR1 attenuated virus production. Our results suggest that enterovirus infection causes the EGR1-mediated upregulation of host miR-141, further lead to the translational switch from cap-dependent to cap-independent protein synthesis in the host cells, an environmental beneficial for viral propagation. This novel mechanism may highlight a new approach for future development of antiviral therapy.
 
Overall design Enteroviruses in the Picornaviridae family are important human pathogens which can cause fatal diseases, including cardiopulmonary failure, aseptic meningitis, paralysis, myocarditis, and encephalomyelitis. Virus infection may induce shutoff of host protein synthesis, particularly in picornavirus, whose protein translation is cap-independent. It is known that poliovirus 2A protease cleaves eIF4G, a scaffold component of mammalian cell translational complex, leading to the shut down of host protein synthesis. Nevertheless, the cleavage of eIF4G may not be sufficient for the complete shutoff of host protein synthesis. Previous studies showed that cleavage of polyA-binding protein (PABP) by viral protease 3C and dephosphorylation of the translational repressor, eIF4E binding protein 1 (4E-BP1), also contribute to this process. The cap-binding protein, eIF4E, is the most crucial factor in determining whether cap-dependent or -independent translation takes place. The mechanism by which viral infection modulates host cell protein synthesis through interfering eIF4E expression is not yet known. miRNAs are a newly discovered class of small non-protein-coding RNAs that may act via endogenous RNA interference. Our understanding of its role in the dynamic interplay between virus and host components is quite limited. Since both virus infection and miRNAs could hinder cellular protein synthesis, whether miRNAs are involved during virus infection in shutting off host protein synthesis is still unknown. To address this issue, we analyze the altered gene and microRNA expression after EV71 infection.

***This submission represents the mRNA expression component of the study only***
 
Contributor(s) Ho B, Yu S, Lee C, Yang P
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Mar 20, 2009
Last update date Mar 25, 2019
Contact name Sung-Liang Yu
E-mail(s) slyu@ntu.edu.tw
Phone 886-2-23958341
Organization name National Taiwan University
Department Clinical Laboratory Sciences and Medical Biotechnology
Lab Microarray Core Facility
Street address Jen Ai Road Section1
City Taipei
ZIP/Postal code 100
Country Taiwan
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (9)
GSM384870 EV0, biological rep1
GSM384871 EV0, biological rep2
GSM384872 EV0, biological rep3
Relations
BioProject PRJNA115861

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE15323_RAW.tar 43.0 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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