Submitted by Sung-Liang Yu (National Taiwan University, Taiwan) on Mar 20 2009
Platform: microarray – [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Pubmed: None listed
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.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM384870 | EV0, biological rep1 | rhabdomyosarcoma cell | uninfected | Uninfected | ||
GSM384871 | EV0, biological rep2 | rhabdomyosarcoma cell | uninfected | Uninfected | ||
GSM384872 | EV0, biological rep3 | rhabdomyosarcoma cell | uninfected | Uninfected | ||
GSM384873 | EV4, biological rep1 | rhabdomyosarcoma cell | 4 hrs | EV71 | Enterovirus A | |
GSM384874 | EV4, biological rep2 | rhabdomyosarcoma cell | 4 hrs | EV71 | Enterovirus A | |
GSM384875 | EV4, biological rep3 | rhabdomyosarcoma cell | 4 hrs | EV71 | Enterovirus A | |
GSM384876 | EV8, biological rep1 | rhabdomyosarcoma cell | 8 hrs | EV71 | Enterovirus A | |
GSM384877 | EV8, biological rep2 | rhabdomyosarcoma cell | 8 hrs | EV71 | Enterovirus A | |
GSM384878 | EV8, biological rep3 | rhabdomyosarcoma cell | 8 hrs | EV71 | Enterovirus A |