title: West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H.
abstract: The complement system, by virtue of its dual effector and priming functions, is a major host defense against pathogens. Flavivirus nonstructural protein (NS)-1 has been speculated to have immune evasion activity, because it is a secreted glycoprotein, binds back to cell surfaces, and accumulates to high levels in the serum of infected patients. Herein, we demonstrate an immunomodulatory function of West Nile virus NS1. Soluble and cell-surface-associated NS1 binds to and recruits the complement regulatory protein factor H, resulting in decreased complement activation in solution and attenuated deposition of C3 fragments and C5b-9 membrane attack complexes on cell surfaces. Accordingly, extracellular NS1 may function to minimize immune system targeting of West Nile virus by decreasing complement recognition of infected cells.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Chung
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Liszewski
authors.forename: Grant
authors.initials: G
authors.lastname: Nybakken
authors.forename: Alan E
authors.initials: AE
authors.lastname: Davis
authors.forename: R Reid
authors.initials: RR
authors.lastname: Townsend
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017242:Complement Factor H / Q000737:chemistry / Q000378:metabolism*; D017244:Complement Factor I / Q000378:metabolism; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D012996:Solutions; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014902:West Nile virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D012996:Solutions; D017361:Viral Nonstructural Proteins; D017242:Complement Factor H; D017244:Complement Factor I