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 W.C. Beasley; C. Todd Davis; Shuliu Zhang; Bradley S. Schneider; Stephen Higgs; Richard M. Kinney; Alan D.T. Barrett

doi:10.1016/j.virol.2006.03.007

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 W.C. Beasley, C. Todd Davis, Shuliu Zhang, Bradley S. Schneider, Stephen Higgs, Richard M. Kinney, Alan D.T. Barrett

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

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 language	English (US)
Pages (from-to)	245-253
Number of pages	9
Journal	Virology
Volume	349
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2006.03.007
State	Published - Jun 5 2006

Keywords

Attenuated phenotype
Cysteine
Flavivirus
NS4B protein
West Nile virus

ASJC Scopus subject areas

Virology

Access to Document

10.1016/j.virol.2006.03.007

Cite this

@article{93ba4a23b268495dae5c4068d808b67a,

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

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.",

keywords = "Attenuated phenotype, Cysteine, Flavivirus, NS4B protein, West Nile virus",

author = "Wicker, {Jason A.} and Whiteman, {Melissa C.} and Beasley, {David W.C.} and Davis, {C. Todd} and Shuliu Zhang and Schneider, {Bradley S.} and Stephen Higgs and Kinney, {Richard M.} and Barrett, {Alan D.T.}",

note = "Funding Information: JAW is supported by NIH T32 AI 7526 and this work was supported, in part, by the Clayton Foundation for Research.",

year = "2006",

month = jun,

day = "5",

doi = "10.1016/j.virol.2006.03.007",

language = "English (US)",

volume = "349",

pages = "245--253",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice

AU - Wicker, Jason A.

AU - Whiteman, Melissa C.

AU - Beasley, David W.C.

AU - Davis, C. Todd

AU - Zhang, Shuliu

AU - Schneider, Bradley S.

AU - Higgs, Stephen

AU - Kinney, Richard M.

AU - Barrett, Alan D.T.

N1 - Funding Information: JAW is supported by NIH T32 AI 7526 and this work was supported, in part, by the Clayton Foundation for Research.

PY - 2006/6/5

Y1 - 2006/6/5

N2 - 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.

AB - 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.

KW - Attenuated phenotype

KW - Cysteine

KW - Flavivirus

KW - NS4B protein

KW - West Nile virus

UR - http://www.scopus.com/inward/record.url?scp=33744465847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744465847&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2006.03.007

DO - 10.1016/j.virol.2006.03.007

M3 - Article

C2 - 16624366

AN - SCOPUS:33744465847

SN - 0042-6822

VL - 349

SP - 245

EP - 253

JO - Virology

JF - Virology

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this