Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0069479
Title: A Single Amino Acid Substitution in the Core Protein of West Nile Virus Increases Resistance to Acidotropic Compounds
Authors: Martín-Acebes M.A.
Blázquez A.-B.
de Oya N.J.
Escribano-Romero E.
Shi P.-Y. 
Saiz J.-C.
Keywords: amino acid
ammonium chloride
concanamycin A
core protein
glutamine
lysine
virus protein
acidification
amino acid substitution
animal experiment
article
controlled study
endosome
female
genetic stability
mouse
nonhuman
nucleotide sequence
pH
phenotype
trans Golgi network
virion
virus entry
virus envelope
West Nile flavivirus
Amino Acid Substitution
Ammonium Chloride
Analysis of Variance
Animals
Blotting, Western
Cercopithecus aethiops
Cricetinae
Drug Resistance, Viral
Fluorescent Antibody Technique
Hydrogen-Ion Concentration
Macrolides
Mice
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Vero Cells
Viral Core Proteins
Virulence
West Nile virus
Issue Date: 2013
Citation: Martín-Acebes M.A., Blázquez A.-B., de Oya N.J., Escribano-Romero E., Shi P.-Y., Saiz J.-C. (2013). A Single Amino Acid Substitution in the Core Protein of West Nile Virus Increases Resistance to Acidotropic Compounds. PLoS ONE 8 (7) : e69479. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0069479
Rights: Attribution 4.0 International
Abstract: West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses. © 2013 Martín-Acebes et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161290
ISSN: 19326203
DOI: 10.1371/journal.pone.0069479
Rights: Attribution 4.0 International
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