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 Citations (Scopus)

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

Fingerprint

West Nile virus
Polymorphism
Viruses
Mental Competency
Viremia
viremia
genetic polymorphism
Corvus brachyrhynchos
Amino Acids
Crows
amino acids
amino acid substitution
Amino Acid Substitution
Phenotype
phenotype
viruses
Virulence
virulence
Sparrows
Passer domesticus

ASJC Scopus subject areas

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

Cite this

Host competence and helicase activity differences exhibited by west nile viral variants expressing NS3-249 amino acid polymorphisms. / Langevin, Stanley A.; Bowen, Richard A.; Reisen, William; Andrade, Christy C.; Ramey, Wanichaya N.; Maharaj, Payal D.; Anishchenko, Michael; Kenney, Joan L.; Duggal, Nisha K.; Romo, Hannah; Bera, Aloke Kumar; Sanders, Todd A.; Bosco-Lauth, Angela; Smith, Janet L.; Kuhn, Richard; Brault, Aaron.

In: PLoS One, Vol. 9, No. 6, e100802, 27.06.2014.

Research output: Contribution to journalArticle

Langevin, SA, Bowen, RA, Reisen, W, Andrade, CC, Ramey, WN, Maharaj, PD, Anishchenko, M, Kenney, JL, Duggal, NK, Romo, H, Bera, AK, Sanders, TA, Bosco-Lauth, A, Smith, JL, 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, vol. 9, no. 6, e100802. https://doi.org/10.1371/journal.pone.0100802
Langevin, Stanley A. ; Bowen, Richard A. ; Reisen, William ; Andrade, Christy C. ; Ramey, Wanichaya N. ; Maharaj, Payal D. ; Anishchenko, Michael ; Kenney, Joan L. ; Duggal, Nisha K. ; Romo, Hannah ; Bera, Aloke Kumar ; Sanders, Todd A. ; Bosco-Lauth, Angela ; Smith, Janet L. ; Kuhn, Richard ; Brault, Aaron. / Host competence and helicase activity differences exhibited by west nile viral variants expressing NS3-249 amino acid polymorphisms. In: PLoS One. 2014 ; Vol. 9, No. 6.
@article{23ca94f3f6194631a388709899f82458,
title = "Host competence and helicase activity differences exhibited by west nile viral variants expressing NS3-249 amino acid polymorphisms",
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.",
author = "Langevin, {Stanley A.} and Bowen, {Richard A.} and William Reisen and Andrade, {Christy C.} and Ramey, {Wanichaya N.} and Maharaj, {Payal D.} and Michael Anishchenko and Kenney, {Joan L.} and Duggal, {Nisha K.} and Hannah Romo and Bera, {Aloke Kumar} and Sanders, {Todd A.} and Angela Bosco-Lauth and Smith, {Janet L.} and Richard Kuhn and Aaron Brault",
year = "2014",
month = "6",
day = "27",
doi = "10.1371/journal.pone.0100802",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Host competence and helicase activity differences exhibited by west nile viral variants expressing NS3-249 amino acid polymorphisms

AU - Langevin, Stanley A.

AU - Bowen, Richard A.

AU - Reisen, William

AU - Andrade, Christy C.

AU - Ramey, Wanichaya N.

AU - Maharaj, Payal D.

AU - Anishchenko, Michael

AU - Kenney, Joan L.

AU - Duggal, Nisha K.

AU - Romo, Hannah

AU - Bera, Aloke Kumar

AU - Sanders, Todd A.

AU - Bosco-Lauth, Angela

AU - Smith, Janet L.

AU - Kuhn, Richard

AU - Brault, Aaron

PY - 2014/6/27

Y1 - 2014/6/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84903386027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903386027&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0100802

DO - 10.1371/journal.pone.0100802

M3 - Article

C2 - 24971589

AN - SCOPUS:84903386027

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e100802

ER -