{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T22:12:47Z","timestamp":1759011167311,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Duck plague caused by the duck plague virus (DPV) is an infectious disease that seriously harms the waterfowl breeding industry. The VP16 protein of \u03b1 herpesvirus can bind to specific <jats:italic>cis<\/jats:italic>-acting elements upstream of the promoter of the immediate-early (IE, \u03b1) gene to promote the transcription of the IE gene, so it is also called the <jats:italic>trans<\/jats:italic>-inducer of IE gene (\u03b1-TIF). However, no studies on DPV \u03b1-TIF have been reported. This study investigated the DPV pUL48, a homolog of HSV-1 VP16, transcriptional activation region, target sequence, and viral protein affecting its transcriptional activation using a dual-luciferase reporter gene detection system, and pUL48 was identified as the \u03b1-TIF of DPV. (1) The regulation of pUL48 on DPV different gene promoters showed that pUL48 could activate all the promoters of IE genes (ICP4, ICP22, and ICP27) but not the promoters of early and late genes. (2) The activity of pUL48 to ICP4 and ICP22 promoters with different upstream lengths showed that pUL48 activated ICP4 and ICP22 promoters by acting on TAATGA (T) TAT element upstream of ICP4 promoter and TAATTATAT element upstream of ICP22 promoter, respectively. (3) Transcriptional activation of IE gene by truncated proteins of different lengths at the N-terminal of pUL48 was detected. The results showed that the transcriptional activation domain of pUL48 was amino acids 1\u201360 at the N-terminal, and amino acids 1\u201320 was its core region. In addition, it was found that pUL14, pUL46, and pUL47 significantly promoted the transcriptional activation of pUL48. The effects of loss of pUL47 and its nuclear localization signal on the nuclear entry and transcriptional activation function of pUL48 were further examined. The results showed that pUL47 could promote the nuclear entry of pUL48 through its nuclear localization signal at positions 40\u201350 and 768\u2013777 amino acids, thus, enhancing the transcriptional activation function of pUL48 and synergistic promotion of viral gene transcription.<\/jats:p>","DOI":"10.3389\/fmicb.2021.795730","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T20:32:13Z","timestamp":1640291533000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Duck Plague Virus pUL48 Protein Activates the Immediate-Early Gene to Initiate the Transcription of the Virus Gene"],"prefix":"10.3389","volume":"12","author":[{"given":"Tong","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dengjian","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingshu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anchun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renyong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xumin","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaqiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dekang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mafeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Xin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanling","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098575","article-title":"Interaction studies of the human and Arabidopsis thaliana Med25-ACID proteins with the herpes simplex virus VP16- and plant-specific Dreb2a transcription factors.","volume":"9","author":"Aguilar","year":"2014","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7850","DOI":"10.1128\/jvi.68.12.7850-7858.1994","article-title":"Varicella-zoster virus (VZV) open reading frame 10 protein, the homolog of the essential herpes simplex virus protein VP16, is dispensable for VZV replication in vitro.","volume":"68","author":"Cohen","year":"1994","journal-title":"J. Virol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/01652176.2017.1298885","article-title":"Duck virus enteritis (duck plague) - a comprehensive update.","volume":"37","author":"Dhama","year":"2017","journal-title":"Vet. Q."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1002\/pro.2951","article-title":"TRIC: capturing the direct cellular targets of promoter-bound transcriptional activators.","volume":"25","author":"Dugan","year":"2016","journal-title":"Protein Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"123","DOI":"10.5511\/plantbiotechnology.14.0121a","article-title":"VP16 fusion efficiently reveals the function of transcriptional repressors in Arabidopsis.","volume":"31","author":"Fujiwara","year":"2014","journal-title":"Plant Biotechnol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"10112","DOI":"10.1128\/jvi.74.21.10112-10121.2000","article-title":"Differences in determinants required for complex formation and transactivation in related VP16 proteins.","volume":"74","author":"Grapes","year":"2000","journal-title":"J. Virol."},{"key":"B7","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1637\/0005-2086(2007)51[546:PSODEV]2.0.CO;2","article-title":"Preliminary study on duck enteritis virus-induced lymphocyte apoptosis in vivo.","volume":"51","author":"Guiping","year":"2007","journal-title":"Avian Dis."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-018-0928-4","article-title":"Molecular characterization of duck enteritis virus UL41 protein.","volume":"15","author":"He","year":"2018","journal-title":"Virol. J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s13365-015-0339-x","article-title":"Bovine herpesvirus 1 regulatory proteins are detected in trigeminal ganglionic neurons during the early stages of stress-induced escape from latency.","volume":"21","author":"Kook","year":"2015","journal-title":"J. Neurovirol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"7108","DOI":"10.1128\/mcb.17.12.7108","article-title":"Concerted activity of host cell factor subregions in promoting stable VP16 complex assembly and preventing interference by the acidic activation domain.","volume":"17","author":"LaBoissi\u00e8re","year":"1997","journal-title":"Mol. Cell Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3937","DOI":"10.1128\/mcb.17.7.3937","article-title":"Interdigitated residues within a small region of VP16 interact with Oct-1, HCF, and DNA.","volume":"17","author":"Lai","year":"1997","journal-title":"Mol. Cell Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"10596","DOI":"10.1021\/ja800975h","article-title":"NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: structural similarities between VP16 and p53.","volume":"130","author":"Langlois","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"D708","DOI":"10.1093\/nar\/gkx932","article-title":"Virus taxonomy: the database of the international committee on taxonomy of viruses (ICTV).","volume":"46","author":"Lefkowitz","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1159\/000452711","article-title":"Identification of the Nuclear Localization Signal Region of Duck Enteritis Virus UL14 and Its Interaction with VP16.","volume":"59","author":"Li","year":"2016","journal-title":"Intervirology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.virol.2009.06.018","article-title":"Molecular characterization of the genome of duck enteritis virus.","volume":"391","author":"Li","year":"2009","journal-title":"Virology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-015-0424-z","article-title":"Duck enteritis virus UL54 is an IE protein primarily located in the nucleus.","volume":"12","author":"Liu","year":"2015","journal-title":"Virol. J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1128\/jvi.74.2.934-943.2000","article-title":"Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency.","volume":"74","author":"Lu","year":"2000","journal-title":"J. Virol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4898","DOI":"10.1128\/jvi.68.8.4898-4909.1994","article-title":"Protein and DNA elements involved in transactivation of the promoter of the bovine herpesvirus (BHV) 1 IE-1 transcription unit by the BHV alpha gene trans-inducing factor.","volume":"68","author":"Misra","year":"1994","journal-title":"J. Viro."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422x-8-365","article-title":"Herpes simplex virus type 1 UL14 tegument protein regulates intracellular compartmentalization of major tegument protein VP16.","volume":"8","author":"Ohta","year":"2011","journal-title":"Virol J."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005877","article-title":"De novo herpes simplex virus VP16 expression gates a dynamic programmatic transition and sets the latent\/lytic balance during acute infection in trigeminal ganglia.","volume":"12","author":"Sawtell","year":"2016","journal-title":"PLoS Pathog."},{"key":"B21","doi-asserted-by":"publisher","first-page":"267","DOI":"10.21775\/cimb.041.267","article-title":"Alphaherpesvirus latency and reactivation with a focus on herpes simplex virus.","volume":"41","author":"Sawtell","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1007\/s13365-011-0065-y","article-title":"VP16 serine 375 is a critical determinant of herpes simplex virus exit from latency in vivo.","volume":"17","author":"Sawtell","year":"2011","journal-title":"J. Neurovirol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1128\/jvi.05981-11","article-title":"Analysis of the interaction between the essential herpes simplex virus 1 tegument proteins VP16 and VP1\/2.","volume":"86","author":"Svobodova","year":"2012","journal-title":"J. Virol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s11262-006-0069-5","article-title":"Sequence and function of canine herpesvirus alpha-transinducing factor and its interaction with an immediate early promoter.","volume":"33","author":"Tyack","year":"2006","journal-title":"Virus Genes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"9566","DOI":"10.1128\/jvi.79.15.9566-9571.2005","article-title":"Determination of interactions between tegument proteins of herpes simplex virus type 1.","volume":"79","author":"Vittone","year":"2005","journal-title":"J. Virol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.virusres.2011.07.004","article-title":"Complete genome sequence of virulent duck enteritis virus (DEV) strain 2085 and comparison with genome sequences of virulent and attenuated DEV strains.","volume":"160","author":"Wang","year":"2011","journal-title":"Virus Res."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01908","article-title":"Alphaherpesvirus major tegument protein VP22: its precise function in the viral life cycle.","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00529-12","article-title":"Complete genomic sequence of Chinese virulent duck enteritis virus.","volume":"86","author":"Wu","year":"2012","journal-title":"J. Virol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.00484","article-title":"Characterization of nucleocytoplasmic shuttling of pseudorabies virus protein UL46.","volume":"7","author":"Xu","year":"2020","journal-title":"Front. Vet. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1007\/s11262-013-1009-9","article-title":"Comparative genomic sequence analysis between a standard challenge strain and a vaccine strain of duck enteritis virus in China.","volume":"48","author":"Yang","year":"2014","journal-title":"Virus Genes"},{"key":"B31","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1007\/s11427-008-0127-4","article-title":"Functional analysis of transcriptional regulation of herpes simplex virus type 1 tegument protein VP22.","volume":"51","author":"Yu","year":"2008","journal-title":"Sci. China C. Life Sci."},{"key":"B32","first-page":"817","article-title":"[Research advances in VP16 of the herpes virus].","volume":"32","author":"Zhang","year":"2016","journal-title":"Bing Du Xue Bao"},{"key":"B33","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1128\/jvi.65.2.829-841.1991","article-title":"Role of herpes simplex virus type 1 UL46 and UL47 in alpha TIF-mediated transcriptional induction: characterization of three viral deletion mutants.","volume":"65","author":"Zhang","year":"1991","journal-title":"J. Virol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41311-0","article-title":"Molecular characterization and antiapoptotic function analysis of the duck plague virus Us5 gene.","volume":"9","author":"Zhao","year":"2019","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.795730\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T20:32:17Z","timestamp":1640291537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.795730\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":34,"alternative-id":["10.3389\/fmicb.2021.795730"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.795730","relation":{},"ISSN":["1664-302X"],"issn-type":[{"type":"electronic","value":"1664-302X"}],"subject":[],"published":{"date-parts":[[2021,12,23]]},"article-number":"795730"}}