A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice.
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 degrees C as well as attenuation of the neuroinvasive and neurovirulence phenotypes in mice.
Wicker
Jason A
JA
Department of Microbiology and Immunology, Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases, and Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, TX 77555-0609, USA.
Whiteman
Melissa C
MC
Beasley
David W C
DW
Davis
C Todd
CT
Zhang
Shuliu
S
Schneider
Bradley S
BS
Higgs
Stephen
S
Kinney
Richard M
RM
Barrett
Alan D T
AD
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006358:Hot Temperature; D007928:Lethal Dose 50; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D010948:Viral Plaque Assay; D014766:Viremia; D014774:Virulence / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics; D014901:West Nile Fever / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology
C080107:NS4B protein, flavivirus; D017361:Viral Nonstructural Proteins; D003545:Cysteine