West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms

Elizabeth A. Dietrich, Stanley A. Langevin, Claire Y.H. Huang, Payal D. Maharaj, Mark J. Delorey, Richard A. Bowen, Richard M. Kinney, Aaron Brault

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

West Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3-249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells.

Original languageEnglish (US)
Article numbere0004938
JournalPLoS Neglected Tropical Diseases
Volume10
Issue number8
DOIs
StatePublished - Aug 22 2016
Externally publishedYes

Fingerprint

West Nile virus
Virulence
Crows
Mutation
Temperature
Mortality
Kenya
Viremia
Threonine
North America
Proline
Viruses
Phenotype
Amino Acids

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Dietrich, E. A., Langevin, S. A., Huang, C. Y. H., Maharaj, P. D., Delorey, M. J., Bowen, R. A., ... Brault, A. (2016). West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms. PLoS Neglected Tropical Diseases, 10(8), [e0004938]. https://doi.org/10.1371/journal.pntd.0004938

West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms. / Dietrich, Elizabeth A.; Langevin, Stanley A.; Huang, Claire Y.H.; Maharaj, Payal D.; Delorey, Mark J.; Bowen, Richard A.; Kinney, Richard M.; Brault, Aaron.

In: PLoS Neglected Tropical Diseases, Vol. 10, No. 8, e0004938, 22.08.2016.

Research output: Contribution to journalArticle

Dietrich, EA, Langevin, SA, Huang, CYH, Maharaj, PD, Delorey, MJ, Bowen, RA, Kinney, RM & Brault, A 2016, 'West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms', PLoS Neglected Tropical Diseases, vol. 10, no. 8, e0004938. https://doi.org/10.1371/journal.pntd.0004938
Dietrich, Elizabeth A. ; Langevin, Stanley A. ; Huang, Claire Y.H. ; Maharaj, Payal D. ; Delorey, Mark J. ; Bowen, Richard A. ; Kinney, Richard M. ; Brault, Aaron. / West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms. In: PLoS Neglected Tropical Diseases. 2016 ; Vol. 10, No. 8.
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