A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice

Jason A. Wicker, Melissa C. Whiteman, David Beasley, C. Todd Davis, Shuliu Zhang, Bradley S. Schneider, Stephen Higgs, Richard M. Kinney, Alan Barrett

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

West Nile virus (WNV) NS4B is a small hydrophobic nonstructural protein that is hypothesized to participate both in viral replication and evasion of host innate immune defenses. The protein has four cysteine residues (residues 102, 120, 227, and 237). Since cysteines are often critical for the function of proteins, each of the four cysteine residues found in WNV NS4B was mutated to serine by site-directed mutagenesis. While three of these substitutions had little effect on replication or mouse virulence phenotypes, the C102S mutation was associated with a temperature-sensitive phenotype at 41 °C as well as attenuation of the neuroinvasive and neurovirulence phenotypes in mice.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalVirology
Volume349
Issue number2
DOIs
StatePublished - Jun 5 2006

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West Nile virus
Amino Acid Substitution
Cysteine
Phenotype
Proteins
Site-Directed Mutagenesis
Serine
Virulence
Mutation
Temperature

Keywords

  • Attenuated phenotype
  • Cysteine
  • Flavivirus
  • NS4B protein
  • West Nile virus

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice. / Wicker, Jason A.; Whiteman, Melissa C.; Beasley, David; Davis, C. Todd; Zhang, Shuliu; Schneider, Bradley S.; Higgs, Stephen; Kinney, Richard M.; Barrett, Alan.

In: Virology, Vol. 349, No. 2, 05.06.2006, p. 245-253.

Research output: Contribution to journalArticle

Wicker, Jason A. ; Whiteman, Melissa C. ; Beasley, David ; Davis, C. Todd ; Zhang, Shuliu ; Schneider, Bradley S. ; Higgs, Stephen ; Kinney, Richard M. ; Barrett, Alan. / A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice. In: Virology. 2006 ; Vol. 349, No. 2. pp. 245-253.
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