| Gene Name | IRF3 |
| HF Protein Name | Interferon regulatory factor 3 |
| HF Function | Produces type I Interferon |
| Uniprot ID | Q14653 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 3661 |
| Host Factor (HF) Name in Paper | IRF3 |
| Gene synonyms | N.A. |
| Ensemble Gene ID | ENSG00000126456 |
| Ensemble Transcript | ENST00000309877 [Q14653-1];ENST00000377139 [Q14653-1];ENST00000442265 [Q14653-5];ENST00000596765 [Q14653-3];ENST00000597198 [Q14653-1];ENST00000599223 [Q14653-2];ENST00000600022 [Q14653-3];ENST00000601291 [Q14653-4] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000978, GO:0000981, GO:0001077, GO:0001078, GO:0001228, GO:0003677, GO:0003712, GO:0005634, GO:0005654, GO:0005737, GO:0005829, GO:0006366, GO:0006915, GO:0006974, GO:0016032, GO:0019904, GO:0031663, GO:0032479, GO:0032480, GO:0032481, GO:0032727, GO:0032728, GO:0035666, GO:0039530, GO:0042802, GO:0042803, GO:0043123, GO:0043330, GO:0043565, GO:0045351, GO:0045358, GO:0045944, GO:0050689, GO:0050715, GO:0051607, GO:0060333, GO:0060337, GO:0060340, GO:0071359, GO:0071888, GO:0097300, |
| MINT ID | Q14653 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 603734 |
| PANTHER ID | PTHR11949 |
| PDB ID(s) | 1J2F, 1QWT, 1T2K, 1ZOQ, 2O61, 2O6G, 2PI0, 3A77, 3QU6, 5JEJ, 5JEK, 5JEL, 5JEM, 5JEO, 5JER, |
| pfam ID | PF00605, PF10401, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Human herpesvirus 1 |
| Virus Short Name | HSV1 |
| Order | Herpesvirales |
| Virus Family | Herpesviridae |
| Virus Subfamily | Alphaherpesvirinae |
| Genus | Simplexvirus |
| Species | Herpes simplex virus 1 |
| Host | Human, mammals |
| Cell Tropism | Primary site of infection: epithelial mucosal cells , latency: remains latent in sensory neurons (ganglions) |
| Associated Disease | Skin vesicles or mucosal ulcers, rarely encephalitis and meningitis |
| Mode of Transmission | Contact, saliva |
| VIPR DB link | http://www.viprbrc.org/brc/vipr_allSpecies_search.do?method=SubmitForm&decorator=herpes |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/91/herpesviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Herpesviridae |
| Paper Title | The Role of Herpes Simplex Virus Type 1 gamma345 in the Regulation of IRF3 Signaling |
| Author's Name | Richard Manivanh, Jesse Mehrbach, David M. Knipe and David A. Leib |
| Journal Name | Journal Of Virology |
| Pubmed ID | 28904192 |
| Abstract | During viral infection, pattern recognition receptors (PRRs) and their associated adaptors recruit TANK-binding kinase 1 (TBK1) to activate interferon regulatory factor 3 (IRF3), resulting in production of type I interferons (IFNs). ICP0 and ICP34.5 are among the proteins encoded by herpes simplex virus 1 (HSV-1) that modulate type I IFN signaling. We constructed a recombinant virus (ΔXX) that lacks amino acids 87 to 106, a portion of the previously described TBK1-binding domain of the gamma34.5 gene (D. Verpooten, Y. Ma, S. Hou, Z. Yan, and B. He, J Biol Chem 284:1097-1105, 2009, https://doi.org/10.1074/JBC.M805905200). These 20 residues are outside the gamma34.5 beclin1-binding domain (BBD) that interacts with beclin1 and regulates autophagy. Unexpectedly, ΔXX showed no deficit in replication in vivo in a variety of tissues and showed virulence comparable to that of wild-type and marker-rescued viruses following intracerebral infection. ΔXX was fully capable of mediating the dephosphorylation of eIF2alpha, and the virus was capable of controlling the phosphorylation of IRF3. In contrast, a null mutant in gamma34.5 failed to control IRF3 phosphorylation due to an inability of the mutant to sustain expression of ICP0. Our data show that while gamma34.5 regulates IRF3 phosphorylation, the TBK1-binding domain itself has no impact on IRF3 phosphorylation or on replication and pathogenesis in mice.IMPORTANCE Interferons (IFNs) are potent activators of a variety of host responses that serve to control virus infections. The Herpesviridae have evolved countermeasures to IFN responses. Herpes simplex virus 1 (HSV-1) encodes the multifunctional neurovirulence protein ICP34.5. In this study, we investigated the biological relevance of the interaction between ICP34.5 and TANK-binding kinase 1 (TBK1), an activator of IFN responses. Here, we establish that although ICP34.5 binds TBK1 under certain conditions through a TBK1-binding domain (TBD), there was no direct impact of the TBD on viral replication or virulence in mice. Furthermore, we showed that activation of IRF3, a substrate of TBK1, was independent of the TBD. Instead, we provided evidence that the ability of ICP34.5 to control IRF3 activation is through its ability to reverse translational shutoff and sustain the expression of other IFN inhibitors encoded by the virus. This work provides new insights into the immunomodulatory functions of ICP34.5. |
| Used Model | HEK-293T and Vero cells |
| DOI | 10.1128/JVI.01156-17 |
