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 Barrett, David Beasley

Research output: Contribution to journalArticle

32 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

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Keywords

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

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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