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

Autor: Joan L. Kenney, Aaron C. Brault, Janet L. Smith, Angela M. Bosco-Lauth, Michael Anishchenko, Richard J. Kuhn, Hannah Romo, Christy C. Andrade, Aloke Kumar Bera, Stanley A. Langevin, Todd A. Sanders, Richard A. Bowen, Nisha K. Duggal, Wanichaya N. Ramey, Payal D. Maharaj, William K. Reisen
Rok vydání: 2014
Předmět:
viruses
lcsh:Medicine
Viral Nonstructural Proteins
Pathology and Laboratory Medicine
Mice
Emerging Viral Diseases
Chlorocebus aethiops
Medicine and Health Sciences
lcsh:Science
Peptide sequence
chemistry.chemical_classification
Genetics
Multidisciplinary
biology
Virulence
Serine Endopeptidases
virus diseases
Amino acid
Pathogens
West Nile virus
RNA Helicases
Sparrows
Research Article
Virulence Factors
Molecular Sequence Data
Viremia
Polymorphism
Single Nucleotide
Microbiology
Virus
Host Specificity
Viral Evolution
Virology
medicine
Animals
Amino Acid Sequence
Vero Cells
Crows
NS3
Evolutionary Biology
lcsh:R
Helicase
Biology and Life Sciences
medicine.disease
Organismal Evolution
Animal Models of Infection
chemistry
Viral replication
Amino Acid Substitution
Microbial Evolution
biology.protein
lcsh:Q
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 6, p e100802 (2014)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: