| Gene Name | C-REL |
| HF Protein Name | Transcription factor C-Rel |
| HF Function | |
| Uniprot ID | Q04864 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 5966 |
| Host Factor (HF) Name in Paper | C-REL |
| Gene synonyms | N.A. |
| Ensemble Gene ID | ENSG00000162924 |
| Ensemble Transcript | ENST00000295025.12 [Q04864-1];ENST00000394479.4 [Q04864-2] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000785, GO:0000978, GO:0000981, GO:0001228, GO:0003700, GO:0005634, GO:0005654, GO:0005737, GO:0005829, GO:0006954, GO:0007249, GO:0010629, GO:0032688, GO:0034097, GO:0038061, GO:0043123, GO:0045087, GO:0045944, GO:0071159, |
| MINT ID | Q04864 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 164910;619652 |
| PANTHER ID | PTHR24169;PTHR24169:SF4 |
| PDB ID(s) | N.A., |
| pfam ID | PF16179, PF00554, |
| Drug Bank ID | N.A., |
| ChEMBL ID | CHEMBL4296310 |
| Organism | Homo sapiens (Human) |
| Virus Name | Japanese encephalitis virus |
| Virus Short Name | JEV |
| Order | Amarillovirales |
| Virus Family | Flaviviridae |
| Virus Subfamily | N.A. |
| Genus | Flavivirus |
| Species | Japanese encephalitis virus |
| Host | Vertebrates |
| Cell Tropism | Neurons |
| Associated Disease | Encephalitis |
| Mode of Transmission | Sexual contact, blood, breast feeding |
| VIPR DB link | https://www.viprbrc.org/brc/vipr_search.do?species=Japanese_encephalitis_virus |
| ICTV DB link | https://ictv.global/report/183/flaviviridae |
| Virus Host DB link |
| Paper Title | Japanese Encephalitis Virus NS1' Protein Interacts with Host CDK1 Protein to Regulate Antiviral Response |
| Author's Name | Qiuyan Li # 1 2 3, Dengyuan Zhou # 1 2 3, Fan Jia 4, Luping Zhang 1 2 3, Usama Ashraf 1 2 3, Yunchuan Li 1 2 3, Hongyu Duan 1 2 3, Yunfeng Song 1 2 3, Huanchun Chen 1 2 3, Shengbo Cao 1 2 3, Jing Ye 1 2 6 |
| Journal Name | Microbiology Spectrum |
| Pubmed ID | 34756071 |
| Abstract | Type I interferon (IFN-I) is a key component of the host innate immune system. To establish efficient replication, viruses have developed several strategies to escape from the host IFN response. Japanese encephalitis virus (JEV) NS1', a larger NS1-related protein, is known to inhibit the mitochondrial antiviral signaling (MAVS)-mediated IFN-β induction by increasing the binding of transcription factors (CREB and c-Rel) to the microRNA 22 (miRNA-22) promoter. However, the mechanism by which NS1' induces the recruitment of CREB and c-Rel onto the miRNA-22 promoter is unknown. Here, we found that JEV NS1' protein interacts with the host cyclin-dependent kinase 1 (CDK1) protein. Mechanistically, NS1' interrupts the CDC25C phosphatase-mediated dephosphorylation of CDK1, which prolongs the phosphorylation status of CDK1 and leads to the inhibition of MAVS-mediated IFN-β induction. Furthermore, the CREB phosphorylation and c-Rel activation through the IκBα phosphorylation were observed to be enhanced upon the augmentation of CDK1 phosphorylation by NS1'. The abrogation of CDK1 activity by a small-molecule inhibitor significantly suppressed the JEV replication in vitro and in vivo. Moreover, the administration of CDK1 inhibitor protected the wild-type mice from JEV-induced lethality but showed no effect on the MAVS-/- mice challenged with JEV. In conclusion, our study provides new insight into the mechanism of JEV immune evasion, which may lead to the development of novel therapeutic options to treat JEV infection. IMPORTANCE Japanese encephalitis virus (JEV) is the main cause of acute human encephalitis in Asia. The unavailability of specific treatment for Japanese encephalitis demands a better understanding of the basic cellular mechanisms that contribute to the onset of disease. The present study identifies a novel interaction between the JEV NS1' protein and the cellular CDK1 protein, which facilitates the JEV replication by dampening the cellular antiviral response. This study sheds light on a novel mechanism of JEV replication, and thus our findings could be employed for developing new therapies against JEV infection. |
| Used Model | BHK-21 ,HELA |
| DOI | 10.1128/Spectrum.01661-21 |
