{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:26:43Z","timestamp":1790544403876,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,3,31]]},"abstract":"<jats:p>\n                    Cowpox virus Brighton red strain (CPV) contains a gene,\n                    <jats:italic>crmD<\/jats:italic>\n                    , which encodes a 320-aa tumor necrosis factor receptor (TNFR) of 44% and 22% identity, respectively, to the CPV TNFR-like proteins, cytokine response modifiers (crm) CrmB and CrmC. The\n                    <jats:italic>crmD<\/jats:italic>\n                    gene was interrupted in three other cowpox strains examined and absent in various other orthopoxviruses; however, four strains of ectromelia virus (ECT) examined contained an intact\n                    <jats:italic>crmD<\/jats:italic>\n                    (97% identity to CPV\n                    <jats:italic>crmD<\/jats:italic>\n                    ) and lacked cognates of\n                    <jats:italic>crmB<\/jats:italic>\n                    and\n                    <jats:italic>crmC<\/jats:italic>\n                    . The protein, CrmD, contains a transport signal; a 151-aa cysteine-rich region with 21 cysteines that align with human TNFRII ligand-binding region cysteines; and C-terminal region sequences that are highly diverged from cellular TNFR C-terminal region sequences involved in signal transduction. Bacterial maltose-binding proteins containing the CPV or ECT CrmD cysteine-rich region bound TNF and lymphotoxin-\u03b1 (LT\u03b1) and blocked their\n                    <jats:italic>in vitro<\/jats:italic>\n                    cytolytic activity. Secreted viral CrmD bound TNF and LT\u03b1 and was detectable after the early stage of replication, using nonreducing conditions, as 60- to 70-kDa predominant and 90- to 250-kDa minor disulfide-linked complexes that were able to be reduced to a 46-kDa form and deglycosylated to a 38-kDa protein. Cells infected with CPV produced extremely low amounts of CrmD compared with ECT. Possessing up to three TNFRs, including CrmD, which is secreted as disulfide-linked complexes in varied amounts by CPV and ECT, likely enhances the dynamics of the immune modulating mechanisms of orthopoxviruses.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.7.3786","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:44Z","timestamp":1027679504000},"page":"3786-3791","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":118,"title":["A third distinct tumor necrosis factor receptor of orthopoxviruses"],"prefix":"10.1073","volume":"95","author":[{"given":"Vladimir N.","family":"Loparev","sequence":"first","affiliation":[{"name":"Poxvirus Section, Viral Exanthems and Herpesvirus Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Department of Molecular Biology and Immunology, St. Louis University, St. Louis, MO 63104; and Department of Microbiology, Duke University, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Poxvirus Section, Viral Exanthems and Herpesvirus Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Department of Molecular Biology and Immunology, St. Louis University, St. Louis, MO 63104; and Department of Microbiology, Duke University, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice C.","family":"Knight","sequence":"additional","affiliation":[{"name":"Poxvirus Section, Viral Exanthems and Herpesvirus Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Department of Molecular Biology and Immunology, St. Louis University, St. Louis, MO 63104; and Department of Microbiology, Duke University, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne Fanelli","family":"Panus","sequence":"additional","affiliation":[{"name":"Poxvirus Section, Viral Exanthems and Herpesvirus Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Department of Molecular Biology and Immunology, St. Louis University, St. Louis, MO 63104; and Department of Microbiology, Duke University, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Ray","sequence":"additional","affiliation":[{"name":"Poxvirus Section, Viral Exanthems and Herpesvirus Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Department of Molecular Biology and Immunology, St. Louis University, St. Louis, MO 63104; and Department of Microbiology, Duke University, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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