Virus Details


VHFID3063

Host Factor Information

Gene Name EIF4E
HF Protein Name Eukaryotic translation initiation factor 4E
HF Function Promotes PV translation
Uniprot ID P06730
Protein Sequence View Fasta Sequence
NCBI Gene ID 1977
Host Factor (HF) Name in Paper eIF4E
Gene synonyms EIF4EL1 EIF4F
Ensemble Gene ID ENSG00000151247
Ensemble Transcript ENST00000280892 [P06730-3];ENST00000450253 [P06730-1];ENST00000505992 [P06730-2]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0000082, GO:0000289, GO:0000339, GO:0000340, GO:0000932, GO:0003723, GO:0003743, GO:0005737, GO:0005829, GO:0005845, GO:0006405, GO:0006406, GO:0006413, GO:0006417, GO:0010494, GO:0016032, GO:0016281, GO:0016442, GO:0019899, GO:0031370, GO:0036464, GO:0045931, GO:0048471, GO:0070062, GO:0070491,
MINT ID P06730
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 133440
PANTHER ID PTHR11960
PDB ID(s) 1IPB, 1IPC, 1WKW, 2GPQ, 2V8W, 2V8X, 2V8Y, 2W97, 3AM7, 3TF2, 3U7X, 4AZA, 4BEA, 4DT6, 4DUM, 4TPW, 4TQB, 4TQC, 4UED, 5EHC, 5EI3, 5EIR, 5EKV, 5GW6, 5T46,
pfam ID PF01652,
Drug Bank ID DB01649, DB02716, DB01960, DB05165,
ChEMBL ID CHEMBL4848
Organism Homo sapiens (Human)

Pathogen Information

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

Publication Information

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