{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:57:23Z","timestamp":1789887443513,"version":"4.0.1"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"18","license":[{"start":{"date-parts":[[2010,9,15]],"date-time":"2010-09-15T00:00:00Z","timestamp":1284508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Poxviruses produce complement regulatory proteins to subvert the host's immune response. Similar to the human pathogen variola virus, ectromelia virus has a limited host range and provides a mouse model where the virus and the host's immune response have coevolved. We previously demonstrated that multiple components (C3, C4, and factor B) of the classical and alternative pathways are required to survive ectromelia virus infection. Complement's role in the innate and adaptive immune responses likely drove the evolution of a virus-encoded virulence factor that regulates complement activation. In this study, we characterized the ectromelia virus inhibitor of complement enzymes (EMICE). Recombinant EMICE regulated complement activation on the surface of CHO cells, and it protected complement-sensitive intracellular mature virions (IMV) from neutralization<jats:italic>in vitro<\/jats:italic>. It accomplished this by serving as a cofactor for the inactivation of C3b and C4b and by dissociating the catalytic domain of the classical pathway C3 convertase. Infected murine cells initiated synthesis of EMICE within 4 to 6 h postinoculation. The levels were sufficient in the supernatant to protect the IMV, upon release, from complement-mediated neutralization. EMICE on the surface of infected murine cells also reduced complement activation by the alternative pathway. In contrast, classical pathway activation by high-titer antibody overwhelmed EMICE's regulatory capacity. These results suggest that EMICE's role is early during infection when it counteracts the innate immune response. In summary, ectromelia virus produced EMICE within a few hours of an infection, and EMICE in turn decreased complement activation on IMV and infected cells.<\/jats:p>","DOI":"10.1128\/jvi.02677-09","type":"journal-article","created":{"date-parts":[[2010,7,8]],"date-time":"2010-07-08T03:10:42Z","timestamp":1278558642000},"page":"9128-9139","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Ectromelia Virus Inhibitor of Complement Enzymes Protects Intracellular Mature Virus and Infected Cells from Mouse Complement"],"prefix":"10.1128","volume":"84","author":[{"given":"Elizabeth A.","family":"Moulton","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Bertram","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanhai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, Saint Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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