{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:32:33Z","timestamp":1784161953667,"version":"3.55.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although smallpox was eradicated as a global illness more than 30 years ago, variola virus and other related pathogenic poxviruses, such as monkeypox, remain potential bioterrorist weapons or could re-emerge as natural infections. Poxviruses express virulence factors that down-modulate the host\u2019s immune system. We previously compared functional profiles of the poxviral complement inhibitors of smallpox, vaccinia, and monkeypox known as SPICE, VCP (or VICE), and MOPICE, respectively. SPICE was the most potent regulator of human complement and attached to cells via glycosaminoglycans. The major goals of the present study were to further characterize the complement regulatory and heparin binding sites of SPICE and to evaluate a mAb that abrogates its function. Using substitution mutagenesis, we established that (1) elimination of the three heparin binding sites severely decreases but does not eliminate glycosaminoglycan binding, (2) there is a hierarchy of activity for heparin binding among the three sites, and (3) complement regulatory sites overlap with each of the three heparin binding motifs. By creating chimeras with interchanges of SPICE and VCP residues, a combination of two SPICE amino acids (H77 plus K120) enhances VCP activity \u223c200-fold. Also, SPICE residue L131 is critical for both complement regulatory function and accounts for the electrophoretic differences between SPICE and VCP. An evolutionary history for these structure-function adaptations of SPICE is proposed. Finally, we identified and characterized a mAb that inhibits the complement regulatory activity of SPICE, MOPICE, and VCP and thus could be used as a therapeutic agent.<\/jats:p>","DOI":"10.4049\/jimmunol.0901366","type":"journal-article","created":{"date-parts":[[2009,8,10]],"date-time":"2009-08-10T21:06:32Z","timestamp":1249938392000},"page":"3150-3159","source":"Crossref","is-referenced-by-count":29,"title":["Smallpox Inhibitor of Complement Enzymes (SPICE): Dissecting Functional Sites and Abrogating Activity"],"prefix":"10.1093","volume":"183","author":[{"given":"M Kathryn","family":"Liszewski","sequence":"first","affiliation":[{"name":"Department of Medicine\/Division of Rheumatology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn K","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Division of Rheumatology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hauhart","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Division of Rheumatology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia J","family":"Fang","sequence":"additional","affiliation":[{"name":"Medical Service, Veterans Administration Medical Center , San Francisco, CA 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Bertram","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Division of Rheumatology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Division of Rheumatology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,9,1]]},"reference":[{"key":"2026012811245573400_R1","first-page":"17","article-title":"Human monkeypox: an emerging zoonotic disease.","volume-title":"Future Microbiol.","year":"2007"},{"key":"2026012811245573400_R2","first-page":"231","article-title":"Host-based antipoxvirus therapeutic strategies: turning the tables.","volume-title":"J. Clin. Invest.","year":"2005"},{"key":"2026012811245573400_R3","first-page":"1279","article-title":"The looming threat of bioterrorism.","volume-title":"Science","year":"1999"},{"key":"2026012811245573400_R4","first-page":"1115","article-title":"Keeping the lock on smallpox.","volume-title":"Nat. Med.","year":"2003"},{"key":"2026012811245573400_R5","first-page":"416","article-title":"A model for a smallpox-vaccination policy.","volume-title":"N. Engl. J. Med.","year":"2003"},{"key":"2026012811245573400_R6","first-page":"189","article-title":"Adverse events occurring after smallpox vaccination.","volume-title":"Semin. Pediatr. Infect. Dis.","year":"2003"},{"key":"2026012811245573400_R7","first-page":"342","article-title":"The detection of monkeypox in humans in the Western Hemisphere (see comment).","volume-title":"N. Engl. J. Med.","year":"2004"},{"key":"2026012811245573400_R8","first-page":"1005","article-title":"Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox.","volume-title":"Nat. Med.","year":"2005"},{"key":"2026012811245573400_R9","first-page":"46","article-title":"Virulence differences between monkeypox virus isolates from West Africa and the Congo Basin.","volume-title":"J. Virol.","year":"2005"},{"key":"2026012811245573400_R10","first-page":"2661","article-title":"A tale of two clades: monkeypox viruses.","volume-title":"J. Gen. Virol.","year":"2005"},{"key":"2026012811245573400_R11","first-page":"263","article-title":"Capripoxviruses: an emerging worldwide threat to sheep, goats and cattle.","volume-title":"Transbound Emerg. Dis.","year":"2008"},{"key":"2026012811245573400_R12","first-page":"11178","article-title":"Discovery of antivirals against smallpox.","volume-title":"Proc. Natl. Acad. Sci. 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