Host competence and helicase activity differences exhibited by west nile viral variants expressing NS3-249 amino acid polymorphisms

Stanley A. Langevin, Richard A. Bowen, William Reisen, Christy C. Andrade, Wanichaya N. Ramey, Payal D. Maharaj, Michael Anishchenko, Joan L. Kenney, Nisha K. Duggal, Hannah Romo, Aloke Kumar Bera, Todd A. Sanders, Angela Bosco-Lauth, Janet L. Smith, Richard Kuhn, Aaron Brault

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A single helicase amino acid substitution, NS3-T249P, has been shown to increase viremia magnitude/mortality in American crows (AMCRs) following West Nile virus (WNV) infection. Lineage/intra-lineage geographic variants exhibit consistent amino acid polymorphisms at this locus; however, the majority of WNV isolates associated with recent outbreaks reported worldwide have a proline at the NS3-249 residue. In order to evaluate the impact of NS3-249 variants on avian and mammalian virulence, multiple amino acid substitutions were engineered into a WNV infectious cDNA (NY99; NS3-249P) and the resulting viruses inoculated into AMCRs, house sparrows (HOSPs) and mice. Differential viremia profiles were observed between mutant viruses in the two bird species; however, the NS3-249P virus produced the highest mean peak viral loads in both avian models. In contrast, this avian modulating virulence determinant had no effect on LD50 or the neurovirulence phenotype in the murine model. Recombinant helicase proteins demonstrated variable helicase and ATPase activities; however, differences did not correlate with avian or murine viremia phenotypes. These in vitro and in vivo data indicate that avian-specific phenotypes are modulated by critical viral-host protein interactions involving the NS3-249 residue that directly influence transmission efficiency and therefore the magnitude of WNV epizootics in nature.

Original languageEnglish (US)
Article numbere100802
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 27 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Langevin, S. A., Bowen, R. A., Reisen, W., Andrade, C. C., Ramey, W. N., Maharaj, P. D., Anishchenko, M., Kenney, J. L., Duggal, N. K., Romo, H., Bera, A. K., Sanders, T. A., Bosco-Lauth, A., Smith, J. L., Kuhn, R., & Brault, A. (2014). Host competence and helicase activity differences exhibited by west nile viral variants expressing NS3-249 amino acid polymorphisms. PLoS One, 9(6), [e100802]. https://doi.org/10.1371/journal.pone.0100802