{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:43:05Z","timestamp":1792784585125,"version":"4.5.0"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 EY09083"],"award-info":[{"award-number":["RO1 EY09083"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Geisel School of Medicine Immunology Program Training Grant","award":["T32 AI007363"],"award-info":[{"award-number":["T32 AI007363"]}]},{"DOI":"10.13039\/100000053","name":"NEI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Virology"],"published-print":{"date-parts":[[2019,3]]},"DOI":"10.1016\/j.virol.2019.01.006","type":"journal-article","created":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T08:00:54Z","timestamp":1546761654000},"page":"23-28","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":36,"special_numbering":"C","title":["The STING agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) stimulates an antiviral state and protects mice against herpes simplex virus-induced neurological disease"],"prefix":"10.1016","volume":"529","author":[{"given":"Stacey","family":"Cer\u00f3n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"North","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean A.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Leib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.virol.2019.01.006_bib1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/ana.24083","article-title":"Herpes simplex virus encephalitis is a trigger of brain autoimmunity","volume":"75","author":"Armangue","year":"2014","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.virol.2019.01.006_bib2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nature10429","article-title":"STING is a direct innate immune sensor of cyclic di-GMP","volume":"478","author":"Burdette","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.virol.2019.01.006_bib3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.molcel.2014.03.040","article-title":"The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling","volume":"54","author":"Cai","year":"2014","journal-title":"Mol. Cell"},{"key":"10.1016\/j.virol.2019.01.006_bib4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.it.2013.10.012","article-title":"Innate antiviral signalling in the central nervous system","volume":"35","author":"Carty","year":"2014","journal-title":"Trends Immunol."},{"key":"10.1016\/j.virol.2019.01.006_bib5","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/emboj.2013.86","article-title":"Species-specific detection of the antiviral small-molecule compound CMA by STING","volume":"32","author":"Cavlar","year":"2013","journal-title":"EMBO J."},{"key":"10.1016\/j.virol.2019.01.006_bib6","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ni.3558","article-title":"Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing","volume":"17","author":"Chen","year":"2016","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.virol.2019.01.006_bib7","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.15252\/embj.201593458","article-title":"HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression","volume":"35","author":"Christensen","year":"2016","journal-title":"EMBO J."},{"key":"10.1016\/j.virol.2019.01.006_bib8","doi-asserted-by":"crossref","first-page":"5216","DOI":"10.4049\/jimmunol.1300097","article-title":"Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid","volume":"190","author":"Conlon","year":"2013","journal-title":"J. Immunol."},{"key":"10.1016\/j.virol.2019.01.006_bib9","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaad.2007.06.027","article-title":"Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management","volume":"57","author":"Fatahzadeh","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"10.1016\/j.virol.2019.01.006_bib10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11908-017-0568-7","article-title":"Herpes Simplex Encephalitis: an Update","volume":"19","author":"Gnann","year":"2017","journal-title":"Curr. Infect. Dis. Rep."},{"key":"10.1016\/j.virol.2019.01.006_bib11","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1128\/AAC.04321-14","article-title":"STING agonists induce an innate antiviral immune response against hepatitis B virus","volume":"59","author":"Guo","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.virol.2019.01.006_bib12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1517\/13543780903540214","article-title":"The development of the tumor vascular-disrupting agent ASA404 (vadimezan, DMXAA): current status and future opportunities","volume":"19","author":"Head","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.virol.2019.01.006_bib13","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/ni.2350","article-title":"Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING","volume":"13","author":"Holm","year":"2012","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.virol.2019.01.006_bib14","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1007\/s00018-010-0605-2","article-title":"The STING pathway and regulation of innate immune signaling in response to DNA pathogens","volume":"68","author":"Ishikawa","year":"2011","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.virol.2019.01.006_bib15","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/nature08476","article-title":"STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity","volume":"461","author":"Ishikawa","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.virol.2019.01.006_bib16","doi-asserted-by":"crossref","first-page":"11752","DOI":"10.1158\/0008-5472.CAN-05-1658","article-title":"Activation of tumor-associated macrophages by the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid induces an effective CD8+ T-cell-mediated antitumor immune response in murine models of lung cancer and mesothelioma","volume":"65","author":"Jassar","year":"2005","journal-title":"Cancer Res."},{"key":"10.1016\/j.virol.2019.01.006_bib17","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.virol.2015.02.009","article-title":"Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity","volume":"479\u2013480","author":"Knipe","year":"2015","journal-title":"Virology"},{"key":"10.1016\/j.virol.2019.01.006_bib18","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1128\/jvi.63.2.759-768.1989","article-title":"Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency","volume":"63","author":"Leib","year":"1989","journal-title":"J. Virol."},{"key":"10.1016\/j.virol.2019.01.006_bib19","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1084\/jem.20082874","article-title":"A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP","volume":"206","author":"McWhirter","year":"2009","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.virol.2019.01.006_bib20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.virol.2013.05.034","article-title":"Synergistic control of herpes simplex virus pathogenesis by IRF-3, and IRF-7 revealed through non-invasive bioluminescence imaging","volume":"444","author":"Murphy","year":"2013","journal-title":"Virology"},{"key":"10.1016\/j.virol.2019.01.006_bib21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nri2937","article-title":"Recognition of herpesviruses by the innate immune system","volume":"11","author":"Paludan","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.virol.2019.01.006_bib22","doi-asserted-by":"crossref","first-page":"11080","DOI":"10.1128\/JVI.00954-15","article-title":"Role of the DNA sensor STING in protection from lethal infection following corneal and intracerebral challenge with herpes simplex virus 1","volume":"89","author":"Parker","year":"2015","journal-title":"J. Virol."},{"key":"10.1016\/j.virol.2019.01.006_bib23","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/rmv.1848","article-title":"Innate immune response during herpes simplex virus encephalitis and development of immunomodulatory strategies","volume":"25","author":"Piret","year":"2015","journal-title":"Rev. Med Virol."},{"issue":"Pt 9","key":"10.1016\/j.virol.2019.01.006_bib24","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1099\/0022-1317-74-9-1859","article-title":"In vivo characterization of site-directed mutations in the promoter of the herpes simplex virus type 1 latency-associated transcripts","volume":"74","author":"Rader","year":"1993","journal-title":"J. Gen. Virol."},{"key":"10.1016\/j.virol.2019.01.006_bib25","doi-asserted-by":"crossref","first-page":"13348","DOI":"10.1038\/ncomms13348","article-title":"Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS","volume":"7","author":"Reinert","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.virol.2019.01.006_bib26","series-title":"Herpes Simplex Viruses","first-page":"2501","author":"Roizman","year":"2007"},{"key":"10.1016\/j.virol.2019.01.006_bib27","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.preteyeres.2012.08.002","article-title":"Herpes keratitis","volume":"32","author":"Rowe","year":"2013","journal-title":"Prog. Retin Eye Res"},{"key":"10.1016\/j.virol.2019.01.006_bib28","doi-asserted-by":"crossref","first-page":"e1005324","DOI":"10.1371\/journal.ppat.1005324","article-title":"Characterization of a novel human-specific STING agonist that elicits antiviral activity against emerging alphaviruses","volume":"11","author":"Sali","year":"2015","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.virol.2019.01.006_bib29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0014-5793(98)00210-5","article-title":"Involvement of the IRF family transcription factor IRF-3 in virus-induced activation of the IFN-beta gene","volume":"425","author":"Sato","year":"1998","journal-title":"FEBS Lett."},{"key":"10.1016\/j.virol.2019.01.006_bib30","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1128\/IAI.00999-10","article-title":"The N-ethyl-N-nitrosourea-induced Goldenticket mouse mutant reveals an essential function of Sting in the in vivo interferon response to Listeria monocytogenes and cyclic dinucleotides","volume":"79","author":"Sauer","year":"2011","journal-title":"Infect. Immun."},{"key":"10.1016\/j.virol.2019.01.006_bib31","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1189\/jlb.0410216","article-title":"The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-beta-mediated antiviral activity in vitro and in vivo","volume":"89","author":"Shirey","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.virol.2019.01.006_bib32","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jneuroim.2017.03.006","article-title":"Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis","volume":"308","author":"Shives","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.virol.2019.01.006_bib33","doi-asserted-by":"crossref","first-page":"e1006976","DOI":"10.1371\/journal.ppat.1006976","article-title":"STING agonists enable antiviral cross-talk between human cells and confer protection against genital herpes in mice","volume":"14","author":"Skouboe","year":"2018","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.virol.2019.01.006_bib34","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/icb.2015.73","article-title":"Battling the spread: herpes simplex virus and encephalitis","volume":"93","author":"Slifer","year":"2015","journal-title":"Immunol. Cell Biol."},{"key":"10.1016\/j.virol.2019.01.006_bib35","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.tim.2012.03.009","article-title":"Viral disruption of the blood-brain barrier","volume":"20","author":"Spindler","year":"2012","journal-title":"Trends Microbiol."},{"key":"10.1016\/j.virol.2019.01.006_bib36","doi-asserted-by":"crossref","first-page":"7020","DOI":"10.1128\/JVI.76.14.7020-7029.2002","article-title":"Herpes simplex virus type 1 origins of DNA replication play no role in the regulation of flanking promoters","volume":"76","author":"Summers","year":"2002","journal-title":"J. Virol."},{"key":"10.1016\/j.virol.2019.01.006_bib37","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1038\/bjc.2013.101","article-title":"Identification of human-selective analogues of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA)","volume":"108","author":"Tijono","year":"2013","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.virol.2019.01.006_bib38","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2165\/00002018-199410020-00003","article-title":"Clinical toxicity of the interferons","volume":"10","author":"Vial","year":"1994","journal-title":"Drug Saf."},{"key":"10.1016\/j.virol.2019.01.006_bib39","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.virusres.2013.01.001","article-title":"HSV-1 strain McKrae is more neuroinvasive than HSV-1 KOS after corneal or vaginal inoculation in mice","volume":"173","author":"Wang","year":"2013","journal-title":"Virus Res."},{"key":"10.1016\/j.virol.2019.01.006_bib40","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1126\/science.1189801","article-title":"c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response","volume":"328","author":"Woodward","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.virol.2019.01.006_bib41","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1001\/jama.296.8.964","article-title":"Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States","volume":"296","author":"Xu","year":"2006","journal-title":"JAMA"},{"key":"10.1016\/j.virol.2019.01.006_bib42","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00280-014-2395-y","article-title":"Efficacy against subcutaneous or intracranial murine GL261 gliomas in relation to the concentration of the vascular-disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), in the brain and plasma","volume":"73","author":"Yung","year":"2014","journal-title":"Cancer Chemother. Pharmacol."}],"container-title":["Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0042682219300066?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0042682219300066?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:47:44Z","timestamp":1758588464000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0042682219300066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":42,"alternative-id":["S0042682219300066"],"URL":"https:\/\/doi.org\/10.1016\/j.virol.2019.01.006","relation":{},"ISSN":["0042-6822"],"issn-type":[{"value":"0042-6822","type":"print"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The STING agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) stimulates an antiviral state and protects mice against herpes simplex virus-induced neurological disease","name":"articletitle","label":"Article Title"},{"value":"Virology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.virol.2019.01.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Inc.","name":"copyright","label":"Copyright"}]}}