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Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection.<\/jats:p>","DOI":"10.1084\/jem.20092545","type":"journal-article","created":{"date-parts":[[2010,3,22]],"date-time":"2010-03-22T21:41:47Z","timestamp":1269294107000},"page":"793-806","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":296,"title":["Antagonism of the complement component C4 by flavivirus nonstructural protein NS1"],"prefix":"10.1084","volume":"207","author":[{"given":"Panisadee","family":"Avirutnan","sequence":"first","affiliation":[{"name":"Department of Medicine 1 , 2 , and 3"},{"name":"Department of Pathology and Immunology 1 , 2 , and 3"},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110 1 , 2 , and 3"},{"name":"Medical Molecular Biology Unit, Department of Research and Development 4 , 5"},{"name":"Department of Immunology, Faculty of 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