Details:

Alternative Title:
PLoS One
Publisher's site:
http://dx.doi.org/10.1371/journal.pone.0100802
Personal Author:
Langevin, Stanley A. ; Bowen, Richard A. ; Reisen, William K. ; Andrade, Christy C. ; Ramey, Wanichaya N. ; ... More +
Langevin, Stanley A. ; Bowen, Richard A. ; Reisen, William K. ; 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 C. Less -
Description:
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.
Subject:
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Amino Acid Sequence
Amino Acid Substitution
Animals
Chlorocebus Aethiops
Crows
Host Specificity
Mice
Molecular Sequence Data
Polymorphism, Single Nucleotide
RNA Helicases
Serine Endopeptidases
Sparrows / Virology
Vero Cells
Viral Nonstructural Proteins
Virulence
West Nile Virus

Source:
PLoS One. 2014; 9(6).
Pubmed ID:
24971589
Pubmed Central ID:
PMC4074097
Document Type:
Journal Article
Funding:
AI061822/AI/NIAID NIH HHS/United States ; R01 AI055607/AI/NIAID NIH HHS/United States ; R01 AI061822/AI/NIAID NIH HHS/United States ; R01-AI55607/AI/NIAID NIH HHS/United States ; UO1 CI000235/CI/NCPDCID CDC HHS/United States
AI061822/AI/NIAID NIH HHS/United States ; R01 AI055607/AI/NIAID NIH HHS/United States ; R01 AI061822/AI/NIAID NIH HHS/United States ; R01-AI55607/AI/NIAID NIH HHS/United States ; UO1 CI000235/CI/NCPDCID CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:12f84d4bbbb002390e7f540111df9b5d8b4a1c778c2d531af9be7174debd96fb
File Type:

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