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Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.<\/jats:p>","DOI":"10.1073\/pnas.0510462103","type":"journal-article","created":{"date-parts":[[2006,3,31]],"date-time":"2006-03-31T20:25:44Z","timestamp":1143836744000},"page":"5995-6000","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":127,"title":["A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus"],"prefix":"10.1073","volume":"103","author":[{"given":"Al\u00ed","family":"Alejo","sequence":"first","affiliation":[{"name":"*Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 2QQ, United Kingdom;"},{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas, Campus de Cantoblanco, 28049 Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Bego\u00f1a","family":"Ruiz-Arg\u00fcello","sequence":"additional","affiliation":[{"name":"*Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 2QQ, United Kingdom;"},{"name":"Centro de Investigaci\u00f3n en Sanidad Animal, Instituto Nacional de Investigaciones Agrarias, Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Ho","sequence":"additional","affiliation":[{"name":"*Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 2QQ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent P.","family":"Smith","sequence":"additional","affiliation":[{"name":"*Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 2QQ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Saraiva","sequence":"additional","affiliation":[{"name":"*Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 2QQ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Alcami","sequence":"additional","affiliation":[{"name":"*Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 2QQ, United Kingdom;"},{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas, Campus de Cantoblanco, 28049 Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,4,11]]},"reference":[{"key":"e_1_3_3_1_2","volume-title":"Smallpox and Its Eradication","author":"Fenner F.","year":"1988","unstructured":"F. 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