{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:25Z","timestamp":1787022205588,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1008239","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R0AI110457"],"award-info":[{"award-number":["R0AI110457"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI065544"],"award-info":[{"award-number":["R01AI065544"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F32AI129352"],"award-info":[{"award-number":["F32AI129352"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1008239","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T13:42:05Z","timestamp":1577367725000},"page":"e1008239","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Resistance to ectromelia virus infection requires cGAS in bone marrow-derived cells which can be bypassed with cGAMP therapy"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-2589","authenticated-orcid":true,"given":"Eric B.","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Montoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2255-7136","authenticated-orcid":true,"given":"Maria","family":"Ferez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colby","family":"Stotesbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6642-5472","authenticated-orcid":true,"given":"Luis J.","family":"Sigal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"ppat.1008239.ref001","doi-asserted-by":"crossref","DOI":"10.1128\/9781555819521","volume-title":"Principles of Virology","author":"J Flint","year":"2015"},{"key":"ppat.1008239.ref002","first-page":"852","article-title":"Animal models of orthopoxvirus infection","volume":"47","author":"JL Chapman","year":"2010","journal-title":"Vet Pathol. 4 ed. SAGE PublicationsSage CA: Los Angeles, CA"},{"key":"ppat.1008239.ref003","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1385\/IR:32:1-3:293","article-title":"Immune regulation of viral infection and vice versa","volume":"32","author":"HW Virgin","year":"2005","journal-title":"Immunol Res"},{"key":"ppat.1008239.ref004","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1099\/vir.0.81090-0","article-title":"Ectromelia virus: the causative agent of mousepox","volume":"86","author":"DJ Esteban","year":"2005","journal-title":"Journal of General Virology. Microbiology Society"},{"key":"ppat.1008239.ref005","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"F McNab","year":"2015","journal-title":"Nature Reviews Immunology. Nature Publishing Group"},{"key":"ppat.1008239.ref006","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: a complex web of host defenses","volume":"32","author":"WM Schneider","year":"2014","journal-title":"Annual Review of Immunology. Annual Reviews"},{"key":"ppat.1008239.ref007","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.coviro.2011.10.008","article-title":"Interferon-stimulated genes and their antiviral effector functions","volume":"1","author":"JW Schoggins","year":"2011","journal-title":"Curr Opin Virol"},{"key":"ppat.1008239.ref008","first-page":"4214","article-title":"Importance of interferons in recovery from mousepox","volume":"67","author":"G Karupiah","year":"1993","journal-title":"Journal of Virology. American Society for Microbiology (ASM)"},{"key":"ppat.1008239.ref009","first-page":"981","article-title":"The orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination","volume":"205","author":"R-H Xu","year":"2008","journal-title":"The Journal of Experimental Medicine. Rockefeller University Press"},{"key":"ppat.1008239.ref010","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.chom.2013.04.015","article-title":"Crosstalk between the Type 1 Interferon and Nuclear Factor Kappa B Pathways Confers Resistance to a Lethal Virus Infection","volume":"13","author":"D Rubio","year":"2013","journal-title":"Cell Host & Microbe"},{"key":"ppat.1008239.ref011","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"O Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ppat.1008239.ref012","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1146\/annurev-immunol-032713-120156","article-title":"Innate immune sensing and signaling of cytosolic nucleic acids","volume":"32","author":"J Wu","year":"2014","journal-title":"Annual Review of Immunology"},{"key":"ppat.1008239.ref013","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-immunol-032414-112240","article-title":"Innate immune pattern recognition: a cell biological perspective","volume":"33","author":"SW Brubaker","year":"2015","journal-title":"Annual Review of Immunology. Annual Reviews"},{"key":"ppat.1008239.ref014","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/ni.3123","article-title":"Control of adaptive immunity by the innate immune system","volume":"16","author":"A Iwasaki","year":"2015","journal-title":"Nature Immunology. Nature Publishing Group"},{"key":"ppat.1008239.ref015","first-page":"75","article-title":"Innate immunity to virus infection","volume":"227","author":"O Takeuchi","year":"2009","journal-title":"Immunol Rev. John Wiley & Sons, Ltd (10.1111)"},{"key":"ppat.1008239.ref016","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.immuni.2015.11.015","article-title":"Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection","volume":"43","author":"R-H Xu","year":"2015","journal-title":"Immunity"},{"key":"ppat.1008239.ref017","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.celrep.2018.06.004","article-title":"Migratory Dendritic Cells, Group 1 Innate Lymphoid Cells, and Inflammatory Monocytes Collaborate to Recruit NK Cells to the Virus-Infected Lymph Node","volume":"24","author":"E Wong","year":"2018","journal-title":"Cell Rep"},{"key":"ppat.1008239.ref018","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.3389\/fimmu.2018.01297","article-title":"The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus","volume":"9","author":"W-Y Cheng","year":"2018","journal-title":"Frontiers in Immunology. Frontiers"},{"key":"ppat.1008239.ref019","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1371\/journal.ppat.0040030","article-title":"A Role for NKG2D in NK Cell\u2013Mediated Resistance to Poxvirus Disease","volume":"4","author":"M Fang","year":"2008","journal-title":"PLoS Pathogens. Public Library of Science"},{"key":"ppat.1008239.ref020","first-page":"13501","article-title":"Characterization of Ectromelia Virus Deficient in EVM036, the Homolog of Vaccinia virus F13L, and Its Application for Rapid Generation of Recombinant Viruses","volume":"86","author":"F Roscoe","year":"2012","journal-title":"Journal of Virology. American Society for Microbiology"},{"key":"ppat.1008239.ref021","doi-asserted-by":"crossref","first-page":"e1000768","DOI":"10.1371\/journal.ppat.1000768","article-title":"Direct Presentation Is Sufficient for an Efficient Anti-Viral CD8+ T Cell Response","volume":"6","author":"R-H Xu","year":"2010","journal-title":"PLoS Pathogens. Public Library of Science"},{"key":"ppat.1008239.ref022","first-page":"6958","article-title":"Chromosome mapping of Rmp-4, a gonad-dependent gene encoding host resistance to mousepox","volume":"69","author":"DG Brownstein","year":"1995","journal-title":"Journal of Virology. American Society for Microbiology (ASM)"},{"key":"ppat.1008239.ref023","first-page":"3236","article-title":"cGAS and Ifi204 cooperate to produce type I IFNs in response to Francisella infection","volume":"194","author":"KM Storek","year":"2015","journal-title":"J Immunol. American Association of Immunologists"},{"key":"ppat.1008239.ref024","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.chom.2011.04.008","article-title":"IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection","volume":"9","author":"N Kerur","year":"2011","journal-title":"Cell Host & Microbe"},{"key":"ppat.1008239.ref025","doi-asserted-by":"crossref","first-page":"14392","DOI":"10.1038\/ncomms14392","article-title":"IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes","volume":"8","author":"JF Almine","year":"2017","journal-title":"Nat Commun. Nature Publishing Group"},{"key":"ppat.1008239.ref026","doi-asserted-by":"crossref","first-page":"14391","DOI":"10.1038\/ncomms14391","article-title":"IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP","volume":"8","author":"KL J\u00f8nsson","year":"2017","journal-title":"Nat Commun. Nature Publishing Group"},{"key":"ppat.1008239.ref027","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1093\/emboj\/17.22.6660","article-title":"Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7","volume":"17","author":"I Mari\u00e9","year":"1998","journal-title":"EMBO J"},{"key":"ppat.1008239.ref028","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1126\/science.1244040","article-title":"Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects","volume":"341","author":"X-D Li","year":"2013","journal-title":"Science. American Association for the Advancement of Science"},{"key":"ppat.1008239.ref029","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.immuni.2011.02.015","article-title":"CD94 Is Essential for NK Cell-Mediated Resistance to a Lethal Viral Disease","volume":"34","author":"M Fang","year":"2011","journal-title":"Immunity"},{"key":"ppat.1008239.ref030","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":"X Cai","year":"2014","journal-title":"Molecular Cell"},{"key":"ppat.1008239.ref031","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":"Q Chen","year":"2016","journal-title":"Nature Immunology. Nature Publishing Group"},{"key":"ppat.1008239.ref032","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.immuni.2014.10.017","article-title":"STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors","volume":"41","author":"S-R Woo","year":"2014","journal-title":"Immunity"},{"key":"ppat.1008239.ref033","first-page":"674","article-title":"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling","volume":"455","author":"H Ishikawa","year":"2008","journal-title":"Nature. Nature Publishing Group"},{"key":"ppat.1008239.ref034","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nri3921","article-title":"STING: infection, inflammation and cancer","volume":"15","author":"GN Barber","year":"2015","journal-title":"Nature Reviews Immunology. Nature Publishing Group"},{"key":"ppat.1008239.ref035","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.chom.2016.03.010","article-title":"A Mouse Model of Zika Virus Pathogenesis","volume":"19","author":"HM Lazear","year":"2016","journal-title":"Cell Host & Microbe"},{"key":"ppat.1008239.ref036","doi-asserted-by":"crossref","first-page":"9100","DOI":"10.1128\/JVI.00316-07","article-title":"Early production of type I interferon during West Nile virus infection: role for lymphoid tissues in IRF3-independent interferon production","volume":"81","author":"N Bourne","year":"2007","journal-title":"Journal of Virology"},{"key":"ppat.1008239.ref037","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1046\/j.1440-1711.2003.01157.x","article-title":"Evasion of innate and adaptive immunity by flaviviruses","volume":"81","author":"MS Diamond","year":"2003","journal-title":"Immunol Cell Biol"},{"key":"ppat.1008239.ref038","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.coviro.2016.01.001","article-title":"Type I interferons in viral control and immune regulation","volume":"16","author":"JR Teijaro","year":"2016","journal-title":"Curr Opin Virol"},{"key":"ppat.1008239.ref039","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.immuni.2013.05.004","article-title":"Immune Sensing of DNA","volume":"38","author":"SR Paludan","year":"2013","journal-title":"Immunity"},{"key":"ppat.1008239.ref040","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.15252\/embj.201488029","article-title":"Listeria monocytogenes induces IFN\u03b2 expression through an IFI16-, cGAS- and STING-dependent pathway","volume":"33","author":"K Hansen","year":"2014","journal-title":"EMBO J. EMBO Press"},{"key":"ppat.1008239.ref041","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fcimb.2017.00169","article-title":"The Central Role of IFI204 in IFN-\u03b2 Release and Autophagy Activation during Mycobacterium bovis Infection","volume":"7","author":"L Chunfa","year":"2017","journal-title":"Front Cell Infect Microbiol. Frontiers"},{"key":"ppat.1008239.ref042","doi-asserted-by":"crossref","first-page":"e1003989","DOI":"10.1371\/journal.ppat.1003989","article-title":"Modified vaccinia virus Ankara triggers type I IFN production in murine conventional dendritic cells via a cGAS\/STING-mediated cytosolic DNA-sensing pathway","volume":"10","author":"P Dai","year":"2014","journal-title":"PLoS Pathogens. Public Library of Science"},{"key":"ppat.1008239.ref043","first-page":"530","article-title":"Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP","volume":"503","author":"A Ablasser","year":"2013","journal-title":"Nature. Nature Publishing Group"},{"key":"ppat.1008239.ref044","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":"LS Reinert","year":"2016","journal-title":"Nat Commun. Nature Publishing Group"},{"key":"ppat.1008239.ref045","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1128\/JVI.02702-13","article-title":"Adenovirus detection by the cGAS\/STING\/TBK1 DNA sensing cascade","volume":"88","author":"E Lam","year":"2014","journal-title":"Journal of Virology"},{"key":"ppat.1008239.ref046","doi-asserted-by":"crossref","first-page":"7789","DOI":"10.1128\/JVI.01040-16","article-title":"cGAS-STING Signaling Regulates Initial Innate Control of Cytomegalovirus Infection","volume":"90","author":"C-WJ Lio","year":"2016","journal-title":"Journal of Virology"},{"key":"ppat.1008239.ref047","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.chom.2015.07.015","article-title":"Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein","volume":"18","author":"J-J Wu","year":"2015","journal-title":"Cell Host & Microbe"},{"key":"ppat.1008239.ref048","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1126\/science.1240933","article-title":"Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses","volume":"341","author":"D Gao","year":"2013","journal-title":"Science. American Association for the Advancement of Science"},{"key":"ppat.1008239.ref049","first-page":"691","article-title":"Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity","volume":"505","author":"JW Schoggins","year":"2014","journal-title":"Nature. Nature Publishing Group"},{"key":"ppat.1008239.ref050","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1158\/2326-6066.CIR-17-0263","article-title":"TNF\u03b1 and Radioresistant Stromal Cells Are Essential for Therapeutic Efficacy of Cyclic Dinucleotide STING Agonists in Nonimmunogenic Tumors","volume":"6","author":"BJ Francica","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"ppat.1008239.ref051","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.it.2017.06.008","article-title":"Langerhans Cells\u2014The Macrophage in Dendritic Cell Clothing","volume":"38","author":"T Doebel","year":"2017","journal-title":"Trends Immunol"},{"key":"ppat.1008239.ref052","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1182\/blood-2007-02-073841","article-title":"Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages","volume":"110","author":"I Klein","year":"2007","journal-title":"Blood"},{"key":"ppat.1008239.ref053","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.jid.2016.05.105","article-title":"Natural STING Agonist as an \u201cIdeal\u201d Adjuvant for Cutaneous Vaccination","volume":"136","author":"J Wang","year":"2016","journal-title":"J Invest Dermatol"},{"key":"ppat.1008239.ref054","doi-asserted-by":"crossref","first-page":"e110150","DOI":"10.1371\/journal.pone.0110150","article-title":"Cyclic GMP-AMP displays mucosal adjuvant activity in mice","volume":"9","author":"I \u0160krnjug","year":"2014","journal-title":"PLoS ONE"},{"key":"ppat.1008239.ref055","first-page":"19049","article-title":"Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response","volume":"6","author":"T Li","year":"2016","journal-title":"Sci Rep. Nature Publishing Group"},{"key":"ppat.1008239.ref056","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.immuni.2018.09.016","article-title":"Tumor-Derived cGAMP Triggers a STING-Mediated Interferon Response in Non-tumor Cells to Activate the NK Cell Response","volume":"49","author":"A Marcus","year":"2018","journal-title":"Immunity"},{"key":"ppat.1008239.ref057","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri980","article-title":"Viral mimicry of cytokines, chemokines and their receptors","volume":"3","author":"A Alcam\u00ed","year":"2003","journal-title":"Nature Reviews Immunology. Nature Publishing Group"},{"key":"ppat.1008239.ref058","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1128\/JVI.02145-17","article-title":"Virulent Poxviruses Inhibit DNA Sensing by Preventing STING Activation","volume":"92","author":"I Georgana","year":"2018","journal-title":"Journal of Virology"},{"key":"ppat.1008239.ref059","first-page":"399","article-title":"IRF7: activation, regulation, modification and function","volume":"12","author":"S Ning","year":"2011","journal-title":"Genes Immun. Nature Publishing Group"},{"issue":"10","key":"ppat.1008239.ref060","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1016\/j.celrep.2019.10.118","article-title":"Langerhans Cells Orchestrate the Protective Antiviral Innate Immune Response in the Lymph Node","volume":"29","author":"E Wong","year":"2019","journal-title":"Cell Rep"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1008239","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1008239","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T13:36:28Z","timestamp":1579613788000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1008239"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Miner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,12,26]]},"references-count":60,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1008239","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,26]]}}}