| Gene Name | ATF3 |
| HF Protein Name | Cyclic AMP-dependent transcription factor ATF-3 |
| HF Function | ATF3 enhances the accumulation of LAT (latency- associated transcript) and maintain the integrity of the neurons harboring latent virus |
| Uniprot ID | P18847 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 467 |
| Host Factor (HF) Name in Paper | ATF3 |
| Gene synonyms | N.A. |
| Ensemble Gene ID | ENSG00000162772 |
| Ensemble Transcript | ENST00000336937 [P18847-4];ENST00000341491 [P18847-1];ENST00000366983 [P18847-3];ENST00000366987 [P18847-1];ENST00000464547 [P18847-3];ENST00000613104 [P18847-5];ENST00000613954 [P18847-5] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000122, GO:0000976, GO:0000977, GO:0000978, GO:0000981, GO:0001078, GO:0001228, GO:0003700, GO:0003714, GO:0005634, GO:0005654, GO:0005730, GO:0006094, GO:0008284, GO:0034198, GO:0035914, GO:0036499, GO:0042802, GO:0042803, GO:0044212, GO:0045944, GO:0046982, GO:0061394, GO:0070373, GO:1903984, GO:1990440, GO:1990622, |
| MINT ID | P18847 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 603148 |
| PANTHER ID | PTHR23351;PTHR23351:SF23 |
| PDB ID(s) | N.A., |
| pfam ID | PF00170, |
| Drug Bank ID | DB00852, |
| 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 | Role of activating transcription factor 3 in the synthesis of latency-associated transcript and maintenance of herpes simplex virus 1 in latent state in ganglia |
| Author's Name | Minfeng Shu, Te Du, Grace Zhou and Bernard Roizman |
| Journal Name | PNAS |
| Pubmed ID | 26305977 |
| Abstract | A key property of herpes simplex viruses (HSVs) is their ability to establish latent infection in sensory or autonomic ganglia and to reactivate on physical, hormonal, or emotional stress. In latently infected ganglia, HSVs express a long noncoding RNA, a latency-associated transcript (LAT), which plays a key role in maintaining latently infected neurons, but not viral proteins. To investigate the events leading to reactivation, we examined the use of ganglionic organ cultures that enable rapid reactivation in medium containing antibody to nerve growth factor (NGF) or delayed reactivation in medium containing NGF and epidermal growth factor (EGF). Here we report the discovery that activating transcription factor 3 (ATF3), a stress response protein, profoundly affects the interaction of HSV with its host. Specifically, (i) ATF3 is induced by stress, such as inhibition of protein synthesis or infection (ii) in infected cells, ATF3 enhances the accumulation of LAT by acting on the response elements in the promoter of the LAT precursor RNA (iii) ATF3 is induced nearly 100-fold in ganglionic organ cultures and (iv) ATF3 plays a key role in the maintenance of the latent state, inasmuch as expression of ATF3 bereft of the C-terminal activation domain acts as a dominant negative factor, inducing HSV gene expression in ganglionic organ cultures harboring latent virus and incubated in medium containing NGF and EGF. Thus, ATF3 is a component of a cluster of cellular proteins that together with LAT maintain the integrity of the neurons harboring latent virus. |
| Used Model | HEp-2, Vero, and HEK 293T |
| DOI | 10.1073/pnas.1515369112 |
