| Gene Name | PYHIN1 |
| HF Protein Name | Pyrin and HIN domain-containing protein 1 |
| HF Function | FIX is an antiviral protein, binds viral DNA upon infection and promotes antiviral cytokines expression |
| Uniprot ID | Q6K0P9 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 149628 |
| Host Factor (HF) Name in Paper | IFIX |
| Gene synonyms | IFIX |
| Ensemble Gene ID | ENSG00000163564 |
| Ensemble Transcript | ENST00000368135 [Q6K0P9-5];ENST00000368138 [Q6K0P9-2];ENST00000368140 [Q6K0P9-1];ENST00000392252 [Q6K0P9-4];ENST00000392254 [Q6K0P9-3] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0007049, GO:0016607, GO:0031625, GO:0031648, GO:0032991, GO:0035457, GO:0043388, GO:0045893, GO:0050821, GO:1900182, GO:1902164, GO:2000060, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 612677 |
| PANTHER ID | N.A. |
| PDB ID(s) | N.A., |
| pfam ID | PF02760, PF02758, |
| 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 | Human antiviral protein IFIX suppresses viral gene expression during HSV-1 infection and is counteracted by virus-induced proteasomal degradation |
| Author's Name | Marni S. Crow and Ileana M. Cristea |
| Journal Name | Molecular and Cellular Proteomics |
| Pubmed ID | 28077445 |
| Abstract | The interferon-inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes expression of antiviral cytokines. How IFIX exerts its host defense functions and whether it is inhibited by the virus remain unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection. We find that IFIX has a dynamic localization during infection that changes from diffuse nuclear and nucleoli distribution in uninfected cells to discrete nuclear puncta early in infection. This is rapidly followed by a reduction in IFIX protein levels. Indeed, using immunoaffinity purification and mass spectrometry, we define IFIX interactions during HSV-1 infection, finding an association with a proteasome subunit and proteins involved in ubiquitin-proteasome processes. Using synchronized HSV-1 infection, microscopy, and proteasome-inhibition experiments, we demonstrate that IFIX co-localizes with nuclear proteasome puncta shortly after 3 h of infection and that its pyrin domain is rapidly degraded in a proteasome-dependent manner. We further demonstrate that, in contrast to several other host defense factors, IFIX degradation is not dependent on the E3 ubiquitin ligase activity of the viral protein ICP0. However, we show IFIX degradation requires immediate-early viral gene expression, suggesting a viral host suppression mechanism. The IFIX interactome also demonstrated its association with transcriptional regulatory proteins, including the 5FMC complex. We validate this interaction using microscopy and reciprocal isolations and determine it is mediated by the IFIX HIN domain. Finally, we show IFIX suppresses immediate-early and early viral gene expression during infection. Altogether, our study demonstrates that IFIX antiviral functions work in part via viral transcriptional suppression and that HSV-1 has acquired mechanisms to block its functions via proteasome-dependent degradation. |
| Used Model | HEK293 cells |
| DOI | 10.1074/mcp.M116.064741 |
