| Gene Name | EIF4A2 |
| HF Protein Name | Eukaryotic initiation factor 4A-II |
| HF Function | Essential for HEV replication |
| Uniprot ID | Q14240 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 1974 |
| Host Factor (HF) Name in Paper | EIF4A2 |
| Gene synonyms | DDX2B EIF4F |
| Ensemble Gene ID | ENSG00000156976 |
| Ensemble Transcript | ENST00000323963 [Q14240-1];ENST00000440191 [Q14240-2] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000289, GO:0003723, GO:0003743, GO:0004004, GO:0004386, GO:0005524, GO:0005730, GO:0005829, GO:0006413, GO:0006446, GO:0010501, GO:0016032, GO:0016281, GO:0016887, GO:0048471, GO:1900260, |
| MINT ID | Q14240 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 601102 |
| PANTHER ID | PTHR24031:SF226 |
| PDB ID(s) | 3BOR, |
| pfam ID | PF00270, PF00271, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Hepatitis E virus |
| Virus Short Name | HEV |
| Order | Unassigned |
| Virus Family | Hepeviridae |
| Virus Subfamily | N.A. |
| Genus | Orthohepevirus |
| Species | Hepatitis E virus |
| Host | Human, pig, wild boar, monkey, some rodents, chicken |
| Cell Tropism | Intestinal tract, hepatocytes and cells in the biliary tract |
| Associated Disease | Hepatitis |
| Mode of Transmission | Zoonosis, fomite |
| VIPR DB link | https://www.viprbrc.org/brc/aboutPathogen.spg?decorator=hepe |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/259/hepeviridae |
| Virus Host DB link | N.A. |
| Paper Title | Requirement of the eukaryotic translation initiation factor 4F complex in hepatitis E virus replication |
| Author's Name | Xinying Zhou, Lei Xu, Yijin Wang, Wenshi Wang, Dave Sprengers, Herold J. Metselaar, Maikel P. Peppelenbosch, and Qiuwei Pan |
| Journal Name | Antiviral Research |
| Pubmed ID | 26526587 |
| Abstract | Hepatitis E virus (HEV) infection, one of the foremost causes of acute hepatitis, is becoming a health problem of increasing magnitude. As other viruses, HEV exploits elements from host cell biochemistry, but we understand little as to which components of the human hepatocellular machinery are perverted for HEV multiplication. It is, however, known that the eukaryotic translation initiation factors 4F(eIF4F) complex, the key regulator of the mRNA-ribosome recruitment phase of translation initiation, serves as an important component for the translation and replication of many viruses. Here we aim to investigate the role of three subunits of the eIF4F complex: eukaryotictranslation initiation factor 4A (eIF4A), eukaryotic translation initiation factor 4G (eIF4G) and eukaryotic translation initiation factor 4E (eIF4E) in HEV replication. We found that efficient replication of HEV requires eIF4A, eIF4G and eIF4E. Consistently, the negative regulatory factors of this complex: programmed cell death 4 (PDCD4) and eIF4E-binding protein 1 (4E-BP1) exert anti-HEV activities, which further illustrates the requirement for eIF4A and eIF4E in supporting HEV replication. Notably, phosphorylation of eIF4E induced by MNK1/2 activation is not involved in HEV replication. Although ribavirin and interferon-alpha (IFN-alpha), the most often-used off-label drugs for treating hepatitis E, interact with this complex, their antiviral activities are independent of eIF4E. In contrast, eIF4E silencing provokes enhanced anti-HEV activity of these compounds. Thus, HEV replication requires eIF4F complex and targeting essential elements of this complex provides important clues for the development of novel antiviral therapy against HEV. |
| Used Model | HuH7 cells |
| DOI | 10.1016/j.antiviral.2015.10.016 |
