{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:32:57Z","timestamp":1792290777577,"version":"4.4.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T00:00:00Z","timestamp":1407974400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1004326","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T19:27:27Z","timestamp":1408044447000},"page":"e1004326","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["EVM005: An Ectromelia-Encoded Protein with Dual Roles in NF-\u03baB Inhibition and Virulence"],"prefix":"10.1371","volume":"10","author":[{"given":"Nicholas","family":"van Buuren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Burles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Schriewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninad","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Mark","family":"Buller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Barry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,8,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared principles in NF-kappaB signaling","volume":"132","author":"MS Hayden","year":"2008","journal-title":"Cell"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","article-title":"Regulation and function of NF-kappaB transcription factors in the immune system","volume":"27","author":"S Vallabhapurapu","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1172\/JCI11918","article-title":"Hostile takeovers: viral appropriation of the NF-kappaB pathway","volume":"107","author":"J Hiscott","year":"2001","journal-title":"J Clin Invest"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1038\/sj.onc.1209941","article-title":"Manipulation of the nuclear factor-kappaB pathway and the innate immune response by viruses","volume":"25","author":"J Hiscott","year":"2006","journal-title":"Oncogene"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.4161\/cc.8.19.9683","article-title":"NFkB inhibitors: strategies from poxviruses","volume":"8","author":"MR Mohamed","year":"2009","journal-title":"Cell Cycle"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"6959","DOI":"10.1038\/sj.onc.1203217","article-title":"Epstein-barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-kappaB","volume":"18","author":"ED Cahir McFarland","year":"1999","journal-title":"Oncogene"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1128\/MMBR.59.3.481-505.1995","article-title":"Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B\/Rel transcription factors","volume":"59","author":"A Roulston","year":"1995","journal-title":"Microbiol Rev"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1089\/jir.2009.0070","article-title":"Paramyxovirus disruption of interferon signal transduction: STATus report","volume":"29","author":"A Ramachandran","year":"2009","journal-title":"J Interferon Cytokine Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"8527","DOI":"10.1128\/JVI.70.12.8527-8533.1996","article-title":"An IkappaB homolog encoded by African swine fever virus provides a novel mechanism for downregulation of proinflammatory cytokine responses in host macrophages","volume":"70","author":"PP Powell","year":"1996","journal-title":"J Virol"},{"key":"ref10","unstructured":"Moss B (1996) Poxviridae: The Viruses and Their Replication. In: B.N. Fields DMK PMH, editor. Fields Virology. 3rd ed. Philadelphia, PA: Lippincott - Raven Publishers."},{"key":"ref11","unstructured":"Fenner F (1996) Poxviruses. In: Fields B, Howley, PM, editor. Fields Virology. 3rd ed. Philadelphia, PA: Lippincott - Raven Publishers."},{"key":"ref12","doi-asserted-by":"crossref","first-page":"6093","DOI":"10.1128\/JVI.77.11.6093-6100.2003","article-title":"Poxvirus immunomodulatory strategies: current perspectives","volume":"77","author":"JB Johnston","year":"2003","journal-title":"J Virol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1146\/annurev.immunol.21.120601.141049","article-title":"Poxviruses and immune evasion","volume":"21","author":"BT Seet","year":"2003","journal-title":"Annu Rev Immunol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0006-291X(91)90929-2","article-title":"T2 open reading frame from the Shope fibroma virus encodes a soluble form of the TNF receptor","volume":"176","author":"CA Smith","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/0042-6822(91)90853-4","article-title":"Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence","volume":"184","author":"C Upton","year":"1991","journal-title":"Virology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"10162","DOI":"10.1073\/pnas.160027697","article-title":"A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling","volume":"97","author":"A Bowie","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1084\/jem.20041442","article-title":"Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence","volume":"201","author":"J Stack","year":"2005","journal-title":"J Exp Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/emboj.2008.143","article-title":"Viral targeting of DEAD box protein 3 reveals its role in TBK1\/IKKepsilon-mediated IRF activation","volume":"27","author":"M Schroder","year":"2008","journal-title":"EMBO J"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1371\/journal.ppat.0040022","article-title":"Inhibition of IkappaB kinase by vaccinia virus virulence factor B14","volume":"4","author":"RA Chen","year":"2008","journal-title":"PLoS Pathog"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"36570","DOI":"10.1074\/jbc.M400567200","article-title":"Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors","volume":"279","author":"G DiPerna","year":"2004","journal-title":"J Biol Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"8676","DOI":"10.1128\/JVI.00935-06","article-title":"Poxviral regulation of the host NF-kappaB response: the vaccinia virus M2L protein inhibits induction of NF-kappaB activation via an ERK2 pathway in virus-infected human embryonic kidney cells","volume":"80","author":"R Gedey","year":"2006","journal-title":"J Virol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1128\/JVI.78.7.3553-3560.2004","article-title":"The vaccinia virus K1L gene product inhibits host NF-kappaB activation by preventing IkappaBalpha degradation","volume":"78","author":"JL Shisler","year":"2004","journal-title":"J Virol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.virol.2007.11.034","article-title":"Characterization of wild-type and mutant vaccinia virus M2L proteins&apos; abilities to localize to the endoplasmic reticulum and to inhibit NF-kappaB activation during infection","volume":"373","author":"O Hinthong","year":"2008","journal-title":"Virology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"e1003183","DOI":"10.1371\/journal.ppat.1003183","article-title":"Poxvirus targeting of E3 ligase beta-TrCP by molecular mimicry: a mechanism to inhibit NF-kappaB activation and promote immune evasion and virulence","volume":"9","author":"DS Mansur","year":"2013","journal-title":"PLoS Pathog"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"9917","DOI":"10.1128\/JVI.00953-08","article-title":"Ectromelia virus encodes a novel family of F-box proteins that interact with the SCF complex","volume":"82","author":"N van Buuren","year":"2008","journal-title":"J Virol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11262-005-1784-z","article-title":"F-box-like domains are present in most poxvirus ankyrin repeat proteins","volume":"31","author":"AA Mercer","year":"2005","journal-title":"Virus Genes"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.18.1.621","article-title":"Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity","volume":"18","author":"M Karin","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0300-9084(01)01237-8","article-title":"Control of IkappaBalpha proteolysis by the ubiquitin-proteasome pathway","volume":"83","author":"K Tanaka","year":"2001","journal-title":"Biochimie"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.1128\/JVI.01835-08","article-title":"Poxvirus host range protein CP77 contains an F-box-like domain that is necessary to suppress NF-kappaB activation by tumor necrosis factor alpha but is independent of its host range function","volume":"83","author":"SJ Chang","year":"2009","journal-title":"J Virol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"10750","DOI":"10.1128\/JVI.79.16.10750-10763.2005","article-title":"Myxoma virus M-T5 protects infected cells from the stress of cell cycle arrest through its interaction with host cell cullin-1","volume":"79","author":"JB Johnston","year":"2005","journal-title":"J Virol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"9045","DOI":"10.1073\/pnas.0900452106","article-title":"Proteomic screening of variola virus reveals a unique NF-kappaB inhibitor that is highly conserved among pathogenic orthopoxviruses","volume":"106","author":"MR Mohamed","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1099\/vir.0.009324-0","article-title":"A truncated two-alpha-helix F-box present in poxvirus ankyrin-repeat proteins is sufficient for binding the SCF1 ubiquitin ligase complex","volume":"90","author":"S Sonnberg","year":"2009","journal-title":"J Gen Virol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"10955","DOI":"10.1073\/pnas.0802042105","article-title":"Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes","volume":"105","author":"S Sonnberg","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.virol.2008.02.018","article-title":"The highly conserved orthopoxvirus 68k ankyrin-like protein is part of a cellular SCF ubiquitin ligase complex","volume":"374","author":"KM Sperling","year":"2008","journal-title":"Virology"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e1000984","DOI":"10.1371\/journal.ppat.1000984","article-title":"Vaccinia virus-encoded ribonucleotide reductase subunits are differentially required for replication and pathogenesis","volume":"6","author":"DB Gammon","year":"2010","journal-title":"PLoS Pathog"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e24643","DOI":"10.1371\/journal.pone.0024643","article-title":"A selectable and excisable marker system for the rapid creation of recombinant poxviruses","volume":"6","author":"JL Rintoul","year":"2011","journal-title":"PLoS One"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev.immunol.16.1.225","article-title":"NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses","volume":"16","author":"S Ghosh","year":"1998","journal-title":"Annu Rev Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"6706","DOI":"10.1038\/sj.onc.1209933","article-title":"Transcriptional regulation via the NF-kappaB signaling module","volume":"25","author":"A Hoffmann","year":"2006","journal-title":"Oncogene"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"9223","DOI":"10.1128\/JVI.00861-09","article-title":"Cowpox virus expresses a novel ankyrin repeat NF-kappaB inhibitor that controls inflammatory cell influx into virus-infected tissues and is critical for virus pathogenesis","volume":"83","author":"MR Mohamed","year":"2009","journal-title":"J Virol"},{"key":"ref40","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":"ref41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.virol.2007.11.036","article-title":"Ectromelia virus BTB\/kelch proteins, EVM150 and EVM167, interact with cullin-3-based ubiquitin ligases","volume":"374","author":"BA Wilton","year":"2008","journal-title":"Virology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1128\/JVI.02923-13","article-title":"Ectromelia Virus Encodes a BTB\/kelch Protein, EVM150, That Inhibits NF-kappaB Signaling","volume":"88","author":"Q Wang","year":"2014","journal-title":"J Virol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"9057","DOI":"10.1073\/pnas.0402949101","article-title":"Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox","volume":"101","author":"G Chaudhri","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref44","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":"J Gen Virol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.virol.2008.11.015","article-title":"Mousepox in the C57BL\/6 strain provides an improved model for evaluating anti-poxvirus therapies","volume":"385","author":"S Parker","year":"2009","journal-title":"Virology"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrmicro2539","article-title":"Modulation of NF-kappaB signalling by microbial pathogens","volume":"9","author":"MM Rahman","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/bbrc.1999.0289","article-title":"IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box\/WD40-repeat proteins, betaTrCP1 and betaTrCP2","volume":"256","author":"H Suzuki","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/0042-6822(91)90047-F","article-title":"Deletion of 55 open reading frames from the termini of vaccinia virus","volume":"180","author":"ME Perkus","year":"1991","journal-title":"Virology"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"4590","DOI":"10.1073\/pnas.0401165101","article-title":"Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge","volume":"101","author":"LS Wyatt","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1128\/JVI.01267-10","article-title":"A vaccinia virus deletion mutant reveals the presence of additional inhibitors of NF-kappaB","volume":"85","author":"K Fagan-Garcia","year":"2011","journal-title":"J Virol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1006\/viro.2001.1090","article-title":"Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-kappaB activation","volume":"288","author":"KL Oie","year":"2001","journal-title":"Virology"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1101\/gad.13.3.270","article-title":"The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro","volume":"13","author":"JT Winston","year":"1999","journal-title":"Genes Dev"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1074\/jbc.M308068200","article-title":"HIV-1 Vpu sequesters beta-transducin repeat-containing protein (betaTrCP) in the cytoplasm and provokes the accumulation of beta-catenin and other SCFbetaTrCP substrates","volume":"279","author":"C Besnard-Guerin","year":"2004","journal-title":"J Biol Chem"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1128\/MCB.23.1.402-413.2003","article-title":"betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932","volume":"23","author":"V Lang","year":"2003","journal-title":"Mol Cell Biol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"7714","DOI":"10.1128\/JVI.00207-06","article-title":"A poxvirus host range protein, CP77, binds to a cellular protein, HMG20A, and regulates its dissociation from the vaccinia virus genome in CHO-K1 cells","volume":"80","author":"JC Hsiao","year":"2006","journal-title":"J Virol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.virol.2004.07.032","article-title":"The cowpox virus host range gene, CP77, affects phosphorylation of eIF2 alpha and vaccinia viral translation in apoptotic HeLa cells","volume":"329","author":"JC Hsiao","year":"2004","journal-title":"Virology"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nrc2396","article-title":"Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer","volume":"8","author":"D Frescas","year":"2008","journal-title":"Nat Rev Cancer"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1128\/JVI.65.1.61-70.1991","article-title":"The target DNA sequence for resolution of poxvirus replicative intermediates is an active late promoter","volume":"65","author":"D Stuart","year":"1991","journal-title":"J Virol"},{"key":"ref59","first-page":"435","article-title":"Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A","volume":"9","author":"JJ Michel","year":"1998","journal-title":"Cell Growth Differ"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1128\/JVI.02061-06","article-title":"Induction of natural killer cell responses by ectromelia virus controls infection","volume":"81","author":"AK Parker","year":"2007","journal-title":"J Virol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e39533","DOI":"10.1371\/journal.pone.0039533","article-title":"Linear fidelity in quantification of anti-viral CD8+ T cells","volume":"7","author":"IE Flesch","year":"2012","journal-title":"PLoS One"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1004326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T07:34:43Z","timestamp":1598168083000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1004326"}},"subtitle":[],"editor":[{"given":"Grant","family":"McFadden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,8,14]]},"references-count":61,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2014,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1004326","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,14]]}}}