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Virology. 2012 Apr 25;426(1):22-33. doi: 10.1016/j.virol.2011.11.022. Epub 2012 Feb 6.

Mutational analysis of the West Nile virus NS4B protein.

Author information

  • 1Department of Microbiology and Immunology, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, TX 77555-0609, USA.

Abstract

West Nile virus NS4B is a small hydrophobic nonstructural protein approximately 27 kDa in size whose function is poorly understood. Amino acid substitutions were introduced into the NS4B protein primarily targeting two distinct regions; the N-terminal domain (residues 35 through 60) and the central hydrophobic domain (residues 95 through 120). Only the NS4B P38G substitution was associated with both temperature-sensitive and small-plaque phenotypes. Importantly, this mutation was found to attenuate neuroinvasiveness greater than 10,000,000-fold and lower viremia titers compared to the wild-type NY99 virus in a mouse model. Full genome sequencing of the NS4B P38G mutant virus revealed two unexpected mutations at NS4B T116I and NS3 N480H (P38G/T116I/N480H), however, neither mutation alone was temperature sensitive or attenuated in mice. Following incubation of P38G/T116I/N480H at 41°C, five mutants encoding compensatory substitutions in the NS4B protein exhibited a reduction in the temperature-sensitive phenotype and reversion to a virulent phenotype in the mouse model.

Copyright © 2011. Published by Elsevier Inc.

PMID:
22314017
[PubMed - indexed for MEDLINE]
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