A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus

Shuliu Zhang, Li Li, Sara E. Woodson, Claire Y.H. Huang, Richard M. Kinney, Alan D.T. Barrett, David W.C. Beasley

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)35-40
Number of pages6
JournalVirology
Volume353
Issue number1
DOIs
StatePublished - Sep 15 2006

Keywords

  • Envelope protein
  • Epitope
  • Flavivirus vaccine
  • Fusion loop
  • Infectious clone
  • Mutagenesis
  • Neuroinvasiveness
  • Neurovirulence
  • Pathogenesis
  • West Nile virus

ASJC Scopus subject areas

  • Virology

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