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Three tumor necrosis factor receptors (TNFRs) have been identified in the poxvirus cowpox virus. Here we report the identification and characterization of a fourth distinct soluble TNFR, named cytokine response modifier E (CrmE), encoded by cowpox virus. The<jats:italic>crmE<\/jats:italic>gene has been sequenced in strains of the orthopoxviruses cowpox virus, ectromelia virus, and camelpox virus, and was found to be active in cowpox virus.<jats:italic>crmE<\/jats:italic>is expressed as a secreted 18-kDa protein with TNF binding activity. CrmE was produced in the baculovirus and vaccinia virus expression systems and was shown to bind human, mouse, and rat TNF, but not human lymphotoxin \u03b1, conjugates of lymphotoxins \u03b1 and \u03b2, or seven other ligands of the TNF superfamily. However, CrmE protects cells only from the cytolytic activity of human TNF. CrmE is a new member of the TNFR superfamily which is expressed as a soluble molecule that blocks the binding of TNF to high-affinity TNFRs on the cell surface. The remarkable finding of a fourth poxvirus-encoded TNFR suggests that modulation of TNF activity is complex and represents a novel viral immune evasion mechanism.<\/jats:p>","DOI":"10.1128\/jvi.75.1.226-233.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:55:53Z","timestamp":1027763753000},"page":"226-233","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":99,"title":["CrmE, a Novel Soluble Tumor Necrosis Factor Receptor Encoded by Poxviruses"],"prefix":"10.1128","volume":"75","author":[{"given":"Margarida","family":"Saraiva","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Alcami","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-73-11-2887"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-80-4-949"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01699-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(96)10051-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90274-G"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.8.4633-4639.1995"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/smvy.1997.0143"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"624","DOI":"10.4049\/jimmunol.160.2.624","article-title":"Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus","volume":"160","author":"Alcami A.","year":"1998","unstructured":"Alcami A. 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