title: A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus.
abstract: Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609, USA.
authors.forename: Shuliu
authors.initials: S
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Sara E
authors.initials: SE
authors.lastname: Woodson
authors.forename: Claire Y-H
authors.initials: CY
authors.lastname: Huang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kinney
authors.forename: Alan D T
authors.initials: AD
authors.lastname: Barrett
authors.forename: David W C
authors.initials: DW
authors.lastname: Beasley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes; D005260:Female; D051379:Mice; D009154:Mutation; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics*; D014774:Virulence; D014901:West Nile Fever / Q000235:genetics*; D014902:West Nile virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D014759:Viral Envelope Proteins