{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:33:02Z","timestamp":1792290782180,"version":"4.4.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:00:00Z","timestamp":1528934400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2018.01297","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:14:52Z","timestamp":1528935292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":69,"title":["The cGas\u2013Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus"],"prefix":"10.3389","volume":"9","author":[{"given":"Wen-Yu","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Bing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-Jie","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Wang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Lin","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Zhong","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,6,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1146\/annurev-immunol-032713-120156","article-title":"Innate immune sensing and signaling of cytosolic nucleic acids","volume":"32","author":"Wu","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nri.2015.8","article-title":"Self-regulation and cross-regulation of pattern-recognition receptor signaling in health and disease","volume":"16","author":"Cao","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nri3479","article-title":"Newly described pattern recognition receptors team up against intracellular pathogens","volume":"13","author":"Broz","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nri.2017.25","article-title":"Multi-receptor detection of individual bacterial products by the innate immune system","volume":"17","author":"Kieser","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/iub.1566","article-title":"cGAS-cGAMP-STING: the three musketeers of cytosolic DNA sensing and signaling","volume":"68","author":"Tao","year":"2016","journal-title":"IUBMB Life"},{"key":"B6","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.mib.2015.12.005","article-title":"Cyclic (di)nucleotides: the common language shared by microbe and host","volume":"30","author":"Gao","year":"2016","journal-title":"Curr Opin Microbiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"8653","DOI":"10.1073\/pnas.0900850106","article-title":"ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization","volume":"106","author":"Sun","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B8","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.immuni.2017.02.011","article-title":"Inflammasome activation triggers caspase-1-mediated cleavage of cGAS to regulate responses to DNA virus infection","volume":"46","author":"Wang","year":"2017","journal-title":"Immunity"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.3389\/fimmu.2017.01078","article-title":"Chronic inflammation in immune aging: role of pattern recognition receptor crosstalk with the telomere complex?","volume":"8","author":"Jose","year":"2017","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/cmi.2017.88","article-title":"Innate immunity in tuberculosis: host defense vs pathogen evasion","volume":"14","author":"Liu","year":"2017","journal-title":"Cell Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.coi.2014.12.011","article-title":"Microbial strategies for antagonizing toll-like-receptor signal transduction","volume":"32","author":"Rosadini","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.coi.2016.10.003","article-title":"Nucleic acid-sensing TLRs: trafficking and regulation","volume":"44","author":"Majer","year":"2017","journal-title":"Curr Opin Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1084\/jem.20161015","article-title":"Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5","volume":"214","author":"Hu","year":"2017","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4415","DOI":"10.4049\/jimmunol.1500859","article-title":"TRIM38 negatively regulates TLR3\/4-mediated innate immune and inflammatory responses by two sequential and distinct mechanisms","volume":"195","author":"Hu","year":"2015","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.cytogfr.2014.05.003","article-title":"MITA\/STING: a central and multifaceted mediator in innate immune response","volume":"25","author":"Ran","year":"2014","journal-title":"Cytokine Growth Factor Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"19341","DOI":"10.1073\/pnas.1110946108","article-title":"Tripartite motif 8 (TRIM8) modulates TNF\u03b1- and IL-1\u03b2-triggered NF-\u03baB activation by targeting TAK1 for K63-linked polyubiquitination","volume":"108","author":"Li","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B17","doi-asserted-by":"publisher","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":"Gao","year":"2013","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/ni.3267","article-title":"Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA","volume":"16","author":"Herzner","year":"2015","journal-title":"Nat Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s13238-016-0320-3","article-title":"DNA sensor cGAS-mediated immune recognition","volume":"7","author":"Xia","year":"2016","journal-title":"Protein Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fimmu.2017.00049","article-title":"Avian Interferons and their antiviral effectors","volume":"8","author":"Santhakumar","year":"2017","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.cytogfr.2014.06.006","article-title":"The mechanism of double-stranded DNA sensing through the cGAS-STING pathway","volume":"25","author":"Shu","year":"2014","journal-title":"Cytokine Growth Factor Rev"},{"key":"B22","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nature12640","article-title":"Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP","volume":"503","author":"Ablasser","year":"2013","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e1004108","DOI":"10.1371\/journal.ppat.1004108","article-title":"Are we there yet? The smallpox research agenda using variola virus","volume":"10","author":"Damon","year":"2014","journal-title":"PLoS Pathog"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1126\/science.345.6200.1010-a","article-title":"Is it time to destroy the smallpox virus?","volume":"345","author":"Arita","year":"2014","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/514544a","article-title":"\u2018Forgotten\u2019 NIH smallpox virus languishes on death row","volume":"514","author":"Reardon","year":"2014","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/v8070203","article-title":"Ectromelia virus disease characterization in the BALB\/c mouse: a surrogate model for assessment of smallpox medical countermeasures","volume":"8","author":"Garver","year":"2016","journal-title":"Viruses"},{"key":"B27","doi-asserted-by":"publisher","first-page":"649","DOI":"10.3201\/eid2304.161041","article-title":"Detection and molecular characterization of zoonotic poxviruses circulating in the Amazon Region of Colombia, 2014","volume":"23","author":"Usme-Ciro","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/bs.ai.2015.10.001","article-title":"The pathogenesis and immunobiology of mousepox","volume":"129","author":"Sigal","year":"2016","journal-title":"Adv Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1089\/vim.2016.0173","article-title":"Innate immune gene transcript level associated with the infection of macrophages with ectromelia virus in two different mouse strains","volume":"30","author":"Dolega","year":"2017","journal-title":"Viral Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1084\/jem.20071854","article-title":"The orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination","volume":"205","author":"Xu","year":"2008","journal-title":"J Exp Med"},{"key":"B31","doi-asserted-by":"publisher","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":"Rubio","year":"2013","journal-title":"Cell Host Microbe"},{"key":"B32","doi-asserted-by":"publisher","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":"Xu","year":"2015","journal-title":"Immunity"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1172\/JCI33940","article-title":"Survival of lethal poxvirus infection in mice depends on TLR9, and therapeutic vaccination provides protection","volume":"118","author":"Samuelsson","year":"2008","journal-title":"J Clin Invest"},{"key":"B34","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/icb.2010.157","article-title":"Evaluating vaccinia virus cytokine co-expression in TLR GKO mice","volume":"89","author":"Sutherland","year":"2011","journal-title":"Immunol Cell Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nature06537","article-title":"TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines","volume":"451","author":"Ishii","year":"2008","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","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":"Dai","year":"2014","journal-title":"PLoS Pathog"},{"key":"B37","doi-asserted-by":"publisher","first-page":"6456180","DOI":"10.1155\/2017\/6456180","article-title":"Comparison of host gene expression profiles in spleen tissues of genetically susceptible and resistant mice during ECTV infection","volume":"2017","author":"Cheng","year":"2017","journal-title":"Biomed Res Int"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.3892\/mmr.2015.4668","article-title":"Molecular cloning and functional characterization of murine toll-like receptor 8","volume":"13","author":"Li","year":"2016","journal-title":"Mol Med Rep"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e52749","DOI":"10.3791\/52749","article-title":"Isolation of murine peritoneal macrophages to carry out gene expression analysis upon toll-like receptors stimulation","volume":"98","author":"Layoun","year":"2015","journal-title":"J Vis Exp"},{"key":"B40","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.mcp.2017.12.001","article-title":"Development of a SYBR Green I real-time PCR for detection and quantitation of orthopoxvirus by using Ectromelia virus","volume":"38","author":"Cheng","year":"2017","journal-title":"Mol Cell Probes"},{"key":"B41","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1084\/jem.20121960","article-title":"Extensive evolutionary and functional diversity among mammalian AIM2-like receptors","volume":"209","author":"Brunette","year":"2012","journal-title":"J Exp Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.4049\/jimmunol.1302718","article-title":"The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-\u03b2 during Chlamydia trachomatis infection","volume":"193","author":"Zhang","year":"2014","journal-title":"J Immunol"},{"key":"B44","doi-asserted-by":"publisher","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":"B45","doi-asserted-by":"publisher","first-page":"3222","DOI":"10.4049\/jimmunol.1700699","article-title":"NEMO-IKK\u03b2 are essential for IRF3 and NF-\u03baB activation in the cGAS-STING pathway","volume":"199","author":"Fang","year":"2017","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/nature12862","article-title":"Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity","volume":"505","author":"Schoggins","year":"2014","journal-title":"Nature"},{"key":"B47","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1128\/JVI.02702-13","article-title":"Adenovirus detection by the cGAS\/STING\/TBK1 DNA sensing cascade","volume":"88","author":"Lam","year":"2014","journal-title":"J Virol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1126\/science.aab3291","article-title":"DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway","volume":"350","author":"Lau","year":"2015","journal-title":"Science"},{"key":"B49","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1111\/febs.13563","article-title":"The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly","volume":"283","author":"Dansako","year":"2016","journal-title":"FEBS J"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e1005546","DOI":"10.1371\/journal.ppat.1005546","article-title":"cGAS senses human cytomegalovirus and induces type I interferon responses in human monocyte-derived cells","volume":"12","author":"Paijo","year":"2016","journal-title":"PLoS Pathog"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e1002934","DOI":"10.1371\/journal.ppat.1002934","article-title":"DENV inhibits type I IFN production in infected cells by cleaving human STING","volume":"8","author":"Aguirre","year":"2012","journal-title":"PLoS Pathog"},{"key":"B52","doi-asserted-by":"publisher","first-page":"7789","DOI":"10.1128\/JVI.01040-16","article-title":"cGAS-STING signaling regulates initial innate control of cytomegalovirus infection","volume":"90","author":"Lio","year":"2016","journal-title":"J Virol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.micinf.2014.10.002","article-title":"The STING controlled cytosolic-DNA activated innate immune pathway and microbial disease","volume":"16","author":"Konno","year":"2014","journal-title":"Microbes Infect"},{"key":"B54","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/ni.2091","article-title":"The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells","volume":"12","author":"Zhang","year":"2011","journal-title":"Nat Immunol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1146\/annurev.immunol.21.120601.141049","article-title":"Poxviruses and immune evasion","volume":"21","author":"Seet","year":"2003","journal-title":"Annu Rev Immunol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1099\/vir.0.81090-0","article-title":"Ectromelia virus: the causative agent of mousepox","volume":"86","author":"Esteban","year":"2005","journal-title":"J Gen Virol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e1004326","DOI":"10.1371\/journal.ppat.1004326","article-title":"EVM005: an ectromelia-encoded protein with dual roles in NF-\u03baB inhibition and virulence","volume":"10","author":"van Buuren","year":"2014","journal-title":"PLoS Pathog"},{"key":"B58","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.virol.2014.08.030","article-title":"Ectromelia virus encodes a family of Ankyrin\/F-box proteins that regulate NF-\u03baB","volume":"46","author":"Burles","year":"2014","journal-title":"Virology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"3236","DOI":"10.4049\/jimmunol.1402764","article-title":"cGAS and Ifi204 cooperate to produce type I IFNs in response to Francisella infection","volume":"194","author":"Storek","year":"2015","journal-title":"J Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1038\/ni.2460","article-title":"The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response","volume":"13","author":"Parvatiyar","year":"2012","journal-title":"Nat Immunol"},{"key":"B61","doi-asserted-by":"publisher","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":"B62","doi-asserted-by":"publisher","first-page":"10680","DOI":"10.1038\/ncomms10680","article-title":"Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses","volume":"7","author":"Holm","year":"2016","journal-title":"Nat Commun"},{"key":"B63","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1111\/2049-632X.12054","article-title":"Quantitative immunophenotypic analysis of antigen-presenting cells involved in ectromelia virus antigen presentation in BALB\/c and C57BL\/6 mice","volume":"68","author":"Szulc-Dabrowska","year":"2013","journal-title":"Pathog Dis"},{"key":"B64","doi-asserted-by":"publisher","first-page":"11170","DOI":"10.1128\/JVI.00256-11","article-title":"The ectromelia virus SPI-2 protein causes lethal mousepox by preventing NK cell responses","volume":"85","author":"Melo-Silva","year":"2011","journal-title":"J Virol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/nature07710","article-title":"AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA","volume":"458","author":"Fernandes-Alnemri","year":"2009","journal-title":"Nature"},{"key":"B66","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/ni.1864","article-title":"The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses","volume":"11","author":"Rathinam","year":"2010","journal-title":"Nat Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.01297\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:14:58Z","timestamp":1528935298000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.01297\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,14]]},"references-count":66,"alternative-id":["10.3389\/fimmu.2018.01297"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2018.01297","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,14]]},"article-number":"1297"}}