title: Human monoclonal antibodies to West Nile virus identify epitopes on the prM protein.
abstract: Hybridoma cell lines (2E8, 8G8 and 5G12) producing fully human monoclonal antibodies (hMAbs) specific for the pre-membrane (prM) protein of West Nile virus (WNV) were prepared using a human fusion partner cell line, MFP-2, and human peripheral blood lymphocytes from a blood donor diagnosed with WNV fever in 2004. Using site-directed mutagenesis of a WNV-like particle (VLP) we identified 4 amino acid residues in the prM protein unique to WNV and important in the binding of these hMAbs to the VLP. Residues V19 and L33 are important epitopes for the binding of all three hMAbs. Mutations at residue, T20 and T24 affected the binding of hMAbs, 8G8 and 5G12 only. These hMAbs did not significantly protect AG129 interferon-deficient mice or Swiss Webster outbred mice from WNV infection.
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, 3150 Rampart Rd., Fort Collins, CO 80521, USA. zpz0@cdc.gov
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Calvert
authors.forename: Gavreel F
authors.initials: GF
authors.lastname: Kalantarov
authors.forename: Gwong-Jen J
authors.initials: GJ
authors.lastname: Chang
authors.forename: Ilya
authors.initials: I
authors.lastname: Trakht
authors.forename: Carol D
authors.initials: CD
authors.lastname: Blair
authors.forename: John T
authors.initials: JT
authors.lastname: Roehrig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus; D007372:Interferons