{"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":1792290782100,"version":"4.4.0"},"reference-count":109,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T00:00:00Z","timestamp":1629590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RTI2018-097581-B-I00"],"award-info":[{"award-number":["RTI2018-097581-B-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF-based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular mechanisms to counteract TNF antiviral action. These include the expression of poxvirus-encoded soluble receptors or proteins able to bind and neutralize TNF and other members of the TNF ligand superfamily, acting as decoy receptors. This article reviews in detail the various TNF decoy receptors identified to date in the genomes from different poxvirus species, with a special focus on their impact on poxvirus pathogenesis and their potential use as therapeutic molecules.<\/jats:p>","DOI":"10.3390\/pathogens10081065","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T22:59:27Z","timestamp":1629673167000},"page":"1065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["TNF Decoy Receptors Encoded by Poxviruses"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-2704","authenticated-orcid":false,"given":"Francisco Javier","family":"Alvarez-de Miranda","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Campus de Cantoblanco, Universidad Aut\u00f3noma de Madrid, Nicol\u00e1s Cabrera 1, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6304-4938","authenticated-orcid":false,"given":"Isabel","family":"Alonso-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Campus de Cantoblanco, Universidad Aut\u00f3noma de Madrid, Nicol\u00e1s Cabrera 1, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3333-6016","authenticated-orcid":false,"given":"Antonio","family":"Alcam\u00ed","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Campus de Cantoblanco, Universidad Aut\u00f3noma de Madrid, Nicol\u00e1s Cabrera 1, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4351-0102","authenticated-orcid":false,"given":"Bruno","family":"Hernaez","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Campus de Cantoblanco, Universidad Aut\u00f3noma de Madrid, Nicol\u00e1s Cabrera 1, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/emboj\/18.8.2119","article-title":"A Casein Kinase I Motif Present in the Cytoplasmic Domain of Members of the Tumour Necrosis Factor Ligand Family Is Implicated in \u201cReverse Signalling\u201d","volume":"18","author":"Watts","year":"1999","journal-title":"EMBO J."},{"key":"ref_2","first-page":"641","article-title":"TNF-\u03b1 Signalling and Inflammation: Interactions between Old Acquaintances","volume":"62","year":"2013","journal-title":"Inflamm. Res. Off. J. Eur. Histamine Res. Soc. Al"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1067\/msy.2000.101584","article-title":"Inflammatory Cytokines and Cell Response in Surgery","volume":"127","author":"Lin","year":"2000","journal-title":"Surgery"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0092-8674(01)00237-9","article-title":"The TNF and TNF Receptor Superfamilies: Integrating Mammalian Biology","volume":"104","author":"Locksley","year":"2001","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nri1184","article-title":"Signalling Pathways of the TNF Superfamily: A Double-Edged Sword","volume":"3","author":"Aggarwal","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/385729a0","article-title":"A Metalloproteinase Disintegrin That Releases Tumour-Necrosis Factor-Alpha from Cells","volume":"385","author":"Black","year":"1997","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0092-8674(90)90158-B","article-title":"A Nonsecretable Cell Surface Mutant of Tumor Necrosis Factor (TNF) Kills by Cell-to-Cell Contact","volume":"63","author":"Perez","year":"1990","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/0092-8674(95)90192-2","article-title":"The Transmembrane Form of Tumor Necrosis Factor Is the Prime Activating Ligand of the 80 KDa Tumor Necrosis Factor Receptor","volume":"83","author":"Grell","year":"1995","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1006\/cyto.1995.0082","article-title":"Dimerization of Chimeric Erythropoietin\/75 KDa Tumour Necrosis Factor (TNF) Receptors Transduces TNF Signals: Necessity for the 75 KDa-TNF Receptor Transmembrane Domain","volume":"7","author":"Declercq","year":"1995","journal-title":"Cytokine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14177","DOI":"10.1074\/jbc.R700052200","article-title":"Molecular Mechanisms of Soluble Cytokine Receptor Generation","volume":"283","author":"Levine","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/intimm\/dxh014","article-title":"Identification and Characterization of a Novel Spliced Variant That Encodes Human Soluble Tumor Necrosis Factor Receptor 2","volume":"16","author":"Lainez","year":"2004","journal-title":"Int. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1126\/science.276.5309.111","article-title":"The Receptor for the Cytotoxic Ligand TRAIL","volume":"276","author":"Pan","year":"1997","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/25387","article-title":"Genomic Amplification of a Decoy Receptor for Fas Ligand in Lung and Colon Cancer","volume":"396","author":"Pitti","year":"1998","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1084\/jem.186.7.1165","article-title":"Cloning and Characterization of TRAIL-R3, a Novel Member of the Emerging TRAIL Receptor Family","volume":"186","author":"Smolak","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_15","first-page":"411","article-title":"Receptor-like Properties of the 26 KDa Transmembrane Form of TNF","volume":"12","author":"Domonkos","year":"2001","journal-title":"Eur. Cytokine Netw."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cytogfr.2004.03.011","article-title":"Ligands Working as Receptors: Reverse Signaling by Members of the TNF Superfamily Enhance the Plasticity of the Immune System","volume":"15","author":"Eissner","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0092-8674(93)90574-A","article-title":"Lymphotoxin Beta, a Novel Member of the TNF Family That Forms a Heteromeric Complex with Lymphotoxin on the Cell Surface","volume":"72","author":"Browning","year":"1993","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9778","DOI":"10.1074\/jbc.271.16.9778","article-title":"Distinct Roles of the Two Tumor Necrosis Factor (TNF) Receptors in Modulating TNF and Lymphotoxin Alpha Effects","volume":"271","author":"Medvedev","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S1074-7613(00)80455-0","article-title":"LIGHT, a New Member of the TNF Superfamily, and Lymphotoxin Alpha Are Ligands for Herpesvirus Entry Mediator","volume":"8","author":"Mauri","year":"1998","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1126\/science.8171322","article-title":"Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin","volume":"264","author":"Goellner","year":"1994","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S1074-7613(00)80292-7","article-title":"Distinct Roles in Lymphoid Organogenesis for Lymphotoxins Alpha and Beta Revealed in Lymphotoxin Beta-Deficient Mice","volume":"6","author":"Koni","year":"1997","journal-title":"Immunity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1126\/science.271.5253.1289","article-title":"Role of Lymphotoxin and the Type I TNF Receptor in the Formation of Germinal Centers","volume":"271","author":"Matsumoto","year":"1996","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1093\/intimm\/mcg094","article-title":"Membrane Lymphotoxin Is Required for Resistance to Theiler\u2019s Virus Infection","volume":"15","author":"Lin","year":"2003","journal-title":"Int. Immunol."},{"key":"ref_24","first-page":"7217","article-title":"A Lymphotoxin-IFN-Beta Axis Essential for Lymphocyte Survival Revealed during Cytomegalovirus Infection","volume":"174","author":"Banks","year":"2005","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1074-7613(00)80295-2","article-title":"Intracellular Inactivation of the Hepatitis B Virus by Cytotoxic T Lymphocytes","volume":"4","author":"Guidotti","year":"1996","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1099\/0022-1317-74-10-2215","article-title":"Participation of Endogenous Tumour Necrosis Factor Alpha in Host Resistance to Cytomegalovirus Infection","volume":"74","author":"Lucin","year":"1993","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1084\/jem.186.9.1591","article-title":"Antiviral Activity of Tumor Necrosis Factor (TNF) Is Mediated via P55 and P75 TNF Receptors","volume":"186","author":"Ruby","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1365-2249.2004.02460.x","article-title":"Protective Effect of Exogenous Recombinant Mouse Interferon-Gamma and Tumour Necrosis Factor-Alpha on Ectromelia Virus Infection in Susceptible BALB\/c Mice","volume":"136","author":"Atrasheuskaya","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"51613","DOI":"10.1074\/jbc.M305633200","article-title":"A Role for Tumor Necrosis Factor Receptor-2 and Receptor-Interacting Protein in Programmed Necrosis and Antiviral Responses","volume":"278","author":"Chan","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1006\/cyto.1995.1021","article-title":"The Role for Host-Immune Factors in the in Vivo Antiviral Effects of Tumour Necrosis Factor","volume":"7","author":"Lidbury","year":"1995","journal-title":"Cytokine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1073\/pnas.88.9.4025","article-title":"Local Production of Tumor Necrosis Factor Encoded by Recombinant Vaccinia Virus Is Effective in Controlling Viral Replication in Vivo","volume":"88","author":"Sambhi","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri980","article-title":"Viral Mimicry of Cytokines, Chemokines and Their Receptors","volume":"3","author":"Alcami","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.1073\/pnas.0510462103","article-title":"A Chemokine-Binding Domain in the Tumor Necrosis Factor Receptor from Variola (Smallpox) Virus","volume":"103","author":"Alejo","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1128\/jvi.68.3.1737-1749.1994","article-title":"Multigenic Evasion of Inflammation by Poxviruses","volume":"68","author":"Palumbo","year":"1994","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1006\/viro.1996.0462","article-title":"Cowpox Virus Genome Encodes a Second Soluble Homologue of Cellular TNF Receptors, Distinct from CrmB, That Binds TNF but Not LT Alpha","volume":"223","author":"Smith","year":"1996","journal-title":"Virology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15973","DOI":"10.1074\/jbc.M115.650119","article-title":"Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors","volume":"290","author":"Pontejo","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1073\/pnas.95.7.3786","article-title":"A Third Distinct Tumor Necrosis Factor Receptor of Orthopoxviruses","volume":"95","author":"Loparev","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1002\/art.24778","article-title":"Outside-to-inside Signaling through Transmembrane Tumor Necrosis Factor Reverses Pathologic Interleukin-1beta Production and Deficient Apoptosis of Rheumatoid Arthritis Monocytes","volume":"60","author":"Meusch","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"26885","DOI":"10.1073\/pnas.2004688117","article-title":"Poxvirus-Encoded TNF Receptor Homolog Dampens Inflammation and Protects from Uncontrolled Lung Pathology during Respiratory Infection","volume":"117","author":"Ng","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1586\/eci.13.14","article-title":"Importance of Reverse Signaling of the TNF Superfamily in Immune Regulation","volume":"9","author":"Duda","year":"2013","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.jmb.2007.06.082","article-title":"Structure of CrmE, a Virus-Encoded Tumour Necrosis Factor Receptor","volume":"372","author":"Graham","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_42","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":"Upton","year":"1991","journal-title":"Virology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1006\/viro.1996.0183","article-title":"Expression of the Myxoma Virus Tumor Necrosis Factor Receptor Homologue and M11L Genes Is Required to Prevent Virus-Induced Apoptosis in Infected Rabbit T Lymphocytes","volume":"218","author":"Macen","year":"1996","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/icb.1996.87","article-title":"M-T2: A Poxvirus TNF Receptor Homologue with Dual Activities","volume":"74","author":"Sedger","year":"1996","journal-title":"Immunol. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9300","DOI":"10.1128\/JVI.02449-05","article-title":"Poxvirus Tumor Necrosis Factor Receptor (TNFR)-like T2 Proteins Contain a Conserved Preligand Assembly Domain That Inhibits Cellular TNFR1-Induced Cell Death","volume":"80","author":"Sedger","year":"2006","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1084\/jem.20020319","article-title":"Inhibition of Type 1 Cytokine-Mediated Inflammation by a Soluble CD30 Homologue Encoded by Ectromelia (Mousepox) Virus","volume":"196","author":"Saraiva","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.virol.2009.01.026","article-title":"Interaction of Human TNF and Beta2-Microglobulin with Tanapox Virus-Encoded TNF Inhibitor, TPV-2L","volume":"386","author":"Rahman","year":"2009","journal-title":"Virology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"22517","DOI":"10.1074\/jbc.M604645200","article-title":"Variation in Ligand Binding Specificities of a Novel Class of Poxvirus-Encoded Tumor Necrosis Factor-Binding Protein","volume":"281","author":"Rahman","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/nsmb.1683","article-title":"Crystal Structure of TNFalpha Complexed with a Poxvirus MHC-Related TNF Binding Protein","volume":"16","author":"Yang","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0968-0004(01)01995-8","article-title":"The Molecular Architecture of the TNF Superfamily","volume":"27","author":"Bodmer","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S1097-2765(00)80207-5","article-title":"Triggering Cell Death: The Crystal Structure of Apo2L\/TRAIL in a Complex with Death Receptor 5","volume":"4","author":"Hymowitz","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1074\/jbc.RA118.005828","article-title":"Insights into Ligand Binding by a Viral Tumor Necrosis Factor (TNF) Decoy Receptor Yield a Selective Soluble Human Type 2 TNF Receptor","volume":"294","author":"Pontejo","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.tibs.2012.06.002","article-title":"An Improved Understanding of TNFL\/TNFR Interactions Using Structure-Based Classifications","volume":"37","author":"Magis","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1126\/science.288.5475.2351","article-title":"A Domain in TNF Receptors That Mediates Ligand-Independent Receptor Assembly and Signaling","volume":"288","author":"Chan","year":"2000","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"ra83","DOI":"10.1126\/scisignal.2000954","article-title":"Solution of the Structure of the TNF-TNFR2 Complex","volume":"3","author":"Mukai","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1126\/science.288.5475.2354","article-title":"Fas Preassociation Required for Apoptosis Signaling and Dominant Inhibition by Pathogenic Mutations","volume":"288","author":"Siegel","year":"2000","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1006\/viro.1994.1539","article-title":"Cowpox Virus Contains Two Copies of an Early Gene Encoding a Soluble Secreted Form of the Type II TNF Receptor","volume":"204","author":"Hu","year":"1994","journal-title":"Virology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1006\/viro.2001.1236","article-title":"Vaccinia Virus CrmE Encodes a Soluble and Cell Surface Tumor Necrosis Factor Receptor That Contributes to Virus Virulence","volume":"292","author":"Reading","year":"2002","journal-title":"Virology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1128\/JVI.75.1.226-233.2001","article-title":"CrmE, a Novel Soluble Tumor Necrosis Factor Receptor Encoded by Poxviruses","volume":"75","author":"Saraiva","year":"2001","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1126\/science.8171323","article-title":"A Lymphotoxin-Beta-Specific Receptor","volume":"264","author":"Crowe","year":"1994","journal-title":"Science"},{"key":"ref_61","first-page":"397","article-title":"Smallpox: Emergence, Global Spread, and Eradication","volume":"15","author":"Fenner","year":"1993","journal-title":"Hist. Philos. Life Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.virol.2014.06.010","article-title":"The Genome Sequence of Ectromelia Virus Naval and Cornell Isolates from Outbreaks in North America","volume":"462\u2013463","author":"Mavian","year":"2014","journal-title":"Virology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10139","DOI":"10.1128\/JVI.77.18.10139-10146.2003","article-title":"Genetic Variability of Immunomodulatory Genes in Ectromelia Virus Isolates Detected by Denaturing High-Performance Liquid Chromatography","volume":"77","author":"Ribas","year":"2003","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.micinf.2010.07.007","article-title":"Modulation of the Host Immune Response by Cowpox Virus","volume":"12","author":"Alzhanova","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/mgme.1999.2878","article-title":"Tumor Necrosis Factor Receptors Encoded by Poxviruses","volume":"67","author":"Cunnion","year":"1999","journal-title":"Mol. Genet. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0042-6822(90)90294-2","article-title":"The Complete DNA Sequence of Vaccinia Virus","volume":"179","author":"Goebel","year":"1990","journal-title":"Virology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/0042-6822(91)90077-O","article-title":"Vaccinia Virus Homologues of the Shope Fibroma Virus Inverted Terminal Repeat Proteins and a Discontinuous ORF Related to the Tumor Necrosis Factor Receptor Family","volume":"180","author":"Howard","year":"1991","journal-title":"Virology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1099\/0022-1317-80-4-949","article-title":"Vaccinia Virus Strains Lister, USSR and Evans Express Soluble and Cell-Surface Tumour Necrosis Factor Receptors","volume":"80","author":"Khanna","year":"1999","journal-title":"J. Gen. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.bbapap.2006.09.006","article-title":"Properties of the Recombinant TNF-Binding Proteins from Variola, Monkeypox, and Cowpox Viruses Are Different","volume":"1764","author":"Gileva","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13964","DOI":"10.1074\/jbc.M601553200","article-title":"Interactions of Tumor Necrosis Factor (TNF) and TNF Receptor Family Members in the Mouse and Human","volume":"281","author":"Bossen","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1099\/jgv.0.000255","article-title":"Poxvirus-Encoded TNF Decoy Receptors Inhibit the Biological Activity of Transmembrane TNF","volume":"96","author":"Pontejo","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1189\/jlb.0703343","article-title":"LPS Resistance in Monocytic Cells Caused by Reverse Signaling through Transmembrane TNF (MTNF) Is Mediated by the MAPK\/ERK Pathway","volume":"75","author":"Kirchner","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1038\/s41467-018-04098-8","article-title":"Chemokines Cooperate with TNF to Provide Protective Anti-Viral Immunity and to Enhance Inflammation","volume":"9","author":"Alejo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Xue, X., Lu, Q., Wei, H., Wang, D., Chen, D., He, G., Huang, L., Wang, H., and Wang, X. (2011). Structural Basis of Chemokine Sequestration by CrmD, a Poxvirus-Encoded Tumor Necrosis Factor Receptor. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002162"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.virusres.2015.02.028","article-title":"Immune Modulation by Virus-Encoded Secreted Chemokine Binding Proteins","volume":"209","author":"Heidarieh","year":"2015","journal-title":"Virus Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1099\/vir.0.055921-0","article-title":"Vaccinia Virus Immune Evasion: Mechanisms, Virulence and Immunogenicity","volume":"94","author":"Smith","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nri.2016.134","article-title":"Mechanisms of Immunomodulation by Mammalian and Viral Decoy Receptors: Insights from Structures","volume":"17","author":"Felix","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4878","DOI":"10.3390\/v7092848","article-title":"Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily","volume":"7","author":"Nelson","year":"2015","journal-title":"Viruses"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1126\/science.2160731","article-title":"A Receptor for Tumor Necrosis Factor Defines an Unusual Family of Cellular and Viral Proteins","volume":"248","author":"Smith","year":"1990","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.4049\/jimmunol.157.10.4486","article-title":"Mutational Analysis of the Ligand-Binding Domain of M-T2 Protein, the Tumor Necrosis Factor Receptor Homologue of Myxoma Virus","volume":"157","author":"Schreiber","year":"1996","journal-title":"J. Immunol."},{"key":"ref_81","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":"Smith","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1128\/jvi.71.3.2171-2181.1997","article-title":"Distinct Domains of M-T2, the Myxoma Virus Tumor Necrosis Factor (TNF) Receptor Homolog, Mediate Extracellular TNF Binding and Intracellular Apoptosis Inhibition","volume":"71","author":"Schreiber","year":"1997","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0165-5728(96)00177-4","article-title":"Myxoma T2 Protein as a Model for Poxvirus TNF Receptor Homologs","volume":"72","author":"McFadden","year":"1997","journal-title":"J. Neuroimmunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1006\/smim.1998.0156","article-title":"CD30: Expression and Function in Health and Disease","volume":"10","author":"Horie","year":"1998","journal-title":"Semin. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8348","DOI":"10.1073\/pnas.122238599","article-title":"Cowpox Virus Encodes a Fifth Member of the Tumor Necrosis Factor Receptor Family: A Soluble, Secreted CD30 Homologue","volume":"99","author":"Panus","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1128\/JVI.79.2.966-977.2005","article-title":"Genome of Deerpox Virus","volume":"79","author":"Afonso","year":"2005","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Alejo, A., Saraiva, M., Ruiz-Arg\u00fcello, M.B., Viejo-Borbolla, A., de Marco, M.F., Salguero, F.J., and Alcami, A. (2009). A Method for the Generation of Ectromelia Virus (ECTV) Recombinants: In Vivo Analysis of ECTV VCD30 Deletion Mutants. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005175"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1073\/pnas.0737244100","article-title":"A Secreted High-Affinity Inhibitor of Human TNF from Tanapox Virus","volume":"100","author":"Brunetti","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1128\/JVI.72.1.460-466.1998","article-title":"Characterization of a Murine Cytomegalovirus Class I Major Histocompatibility Complex (MHC) Homolog: Comparison to MHC Molecules and to the Human Cytomegalovirus MHC Homolog","volume":"72","author":"Chapman","year":"1998","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/386510a0","article-title":"Inhibition of Natural Killer Cells by a Cytomegalovirus MHC Class I Homologue in Vivo","volume":"386","author":"Farrell","year":"1997","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/viro.1998.9390","article-title":"Domain Structure, Intracellular Trafficking, and Beta2-Microglobulin Binding of a Major Histocompatibility Complex Class I Homolog Encoded by Molluscum Contagiosum Virus","volume":"250","author":"Senkevich","year":"1998","journal-title":"Virology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1128\/JVI.76.2.783-790.2002","article-title":"The Genome of Swinepox Virus","volume":"76","author":"Afonso","year":"2002","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.clim.2007.08.013","article-title":"TNFalpha Blockade in Human Diseases: Mechanisms and Future Directions","volume":"126","author":"Wong","year":"2008","journal-title":"Clin. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1478-6354-13-S1-S5","article-title":"Advances in Rheumatology: New Targeted Therapeutics","volume":"13","author":"Tak","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.cyto.2016.08.014","article-title":"Molecular Mechanisms of Action of Anti-TNF-\u03b1 Agents - Comparison among Therapeutic TNF-\u03b1 Antagonists","volume":"101","author":"Mitoma","year":"2018","journal-title":"Cytokine"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0025-6196(11)60839-2","article-title":"Fungal Infections Complicating Tumor Necrosis Factor Alpha Blockade Therapy","volume":"83","author":"Tsiodras","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.3899\/jrheum.110373","article-title":"Incidence of Tuberculosis among Korean Patients with Ankylosing Spondylitis Who Are Taking Tumor Necrosis Factor Blockers","volume":"38","author":"Kim","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Yaron, J.R., Zhang, L., Guo, Q., Burgin, M., Schutz, L.N., Awo, E., Wise, L., Krause, K.L., Ildefonso, C.J., and Kwiecien, J.M. (2020). Deriving Immune Modulating Drugs from Viruses\u2014A New Class of Biologics. J. Clin. Med., 9.","DOI":"10.3390\/jcm9040972"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"72","DOI":"10.2174\/1389201015666141126114945","article-title":"TNF Binding Protein of Variola Virus Acts as a TNF Antagonist at Epicutaneous Application","volume":"16","author":"Gileva","year":"2015","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"910","DOI":"10.2174\/1389201019666181029111011","article-title":"Anti-Inflammatory Effects of Variola Virus TNF Decoy Receptor in an Experimental Model of Contact Dermatitis","volume":"19","author":"Viazovaia","year":"2018","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1134\/S160767291604013X","article-title":"The Gene Therapy of Collagen-Induced Arthritis in Rats by Intramuscular Administration of the Plasmid Encoding TNF-Binding Domain of Variola Virus CrmB Protein","volume":"469","author":"Shchelkunov","year":"2016","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3389\/fphar.2019.00184","article-title":"Triggering the Resolution of Immune Mediated Inflammatory Diseases: Can Targeting Leukocyte Migration Be the Answer?","volume":"10","author":"Hopkin","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Alejo, A., S\u00e1nchez, C., Amu, S., Fallon, P.G., and Alcam\u00ed, A. (2019). Addition of a Viral Immunomodulatory Domain to Etanercept Generates a Bifunctional Chemokine and TNF Inhibitor. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010025"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1126\/science.1243364","article-title":"Nonredundant Function of Soluble LT\u03b13 Produced by Innate Lymphoid Cells in Intestinal Homeostasis","volume":"342","author":"Kruglov","year":"2013","journal-title":"Science"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nri3406","article-title":"Lymphotoxin Signalling in Immune Homeostasis and the Control of Microorganisms","volume":"13","author":"Upadhyay","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","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":"ref_107","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1006\/viro.1998.9123","article-title":"The Complete Genomic Sequence of the Modified Vaccinia Ankara Strain: Comparison with Other Orthopoxviruses","volume":"244","author":"Antoine","year":"1998","journal-title":"Virology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1099\/0022-1317-79-5-1159","article-title":"Modified Vaccinia Virus Ankara Undergoes Limited Replication in Human Cells and Lacks Several Immunomodulatory Proteins: Implications for Use as a Human Vaccine","volume":"79","author":"Blanchard","year":"1998","journal-title":"J. Gen. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11230","DOI":"10.1128\/JVI.74.23.11230-11239.2000","article-title":"The Vaccinia Virus Soluble Alpha\/Beta Interferon (IFN) Receptor Binds to the Cell Surface and Protects Cells from the Antiviral Effects of IFN","volume":"74","author":"Symons","year":"2000","journal-title":"J. Virol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/8\/1065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:49:00Z","timestamp":1760165340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/8\/1065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,22]]},"references-count":109,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["pathogens10081065"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10081065","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,22]]}}}