Virus Name | Polio Virus |
Virus Short Name | PV |
Order | Picornavirales |
Virus Family | Picornaviridae |
Virus Subfamily | N.A. |
Genus | Enterovirus |
Species | Enterovirus C |
Host | Human, mammals |
Cell Tropism | The gastrointestinal tract |
Associated Disease | Poliomyelitis |
Mode of Transmission | Either fecal-oral or respiratory |
VIPR DB link | https://www.viprbrc.org/brc/home.spg?decorator=picorna |
ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/234/picornaviridae |
Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Picornaviridae |
Paper Title | Cellular cap-binding protein, eIF4E, promotes picornavirus genome restructuring and translation |
Author's Name | Brian C. Avanzinoa, Gabriele Fuchsb, and Christopher S. Fraser |
Journal Name | PNAS |
Pubmed ID | 28827335 |
Abstract | Picornaviruses use internal ribosome entry sites (IRESs) to translate their genomes into protein. A typical feature of these IRESs is their ability to bind directly to the eukaryotic initiation factor (eIF) 4G component of the eIF4F cap-binding complex. Remarkably, the hepatitis A virus (HAV) IRES requires eIF4E for its translation, but no mechanism has been proposed to explain this. Here we demonstrate that eIF4E regulates HAV IRES-mediated translation by two distinct mechanisms. First, eIF4E binding to eIF4G generates a high-affinity binding conformation of the eIF4F complex for the IRES. Second, eIF4E binding to eIF4G strongly stimulates the rate of duplex unwinding by eIF4A on the IRES. Our data also reveal that eIF4E promotes eIF4F binding and increases the rate of restructuring of the poliovirus (PV) IRES. This provides a mechanism to explain why PV IRES-mediated translation is stimulated by eIF4E availability in nuclease-treated cell-free extracts. Using a PV replicon and purified virion RNA, we also show that eIF4E promotes the rate of eIF4G cleavage by the 2A protease. Finally, we show that cleavage of eIF4G by the poliovirus 2A protease generates a high-affinity IRES binding truncation of eIF4G that stimulates eIF4A duplex unwinding independently of eIF4E. Therefore, our data reveal how picornavirusIRESs use eIF4E-dependent and -independent mechanisms to promote their translation. |
Used Model | N.A. |
DOI | 10.1073/pnas.1704390114 |