Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0069479
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dc.titleA Single Amino Acid Substitution in the Core Protein of West Nile Virus Increases Resistance to Acidotropic Compounds
dc.contributor.authorMartín-Acebes M.A.
dc.contributor.authorBlázquez A.-B.
dc.contributor.authorde Oya N.J.
dc.contributor.authorEscribano-Romero E.
dc.contributor.authorShi P.-Y.
dc.contributor.authorSaiz J.-C.
dc.date.accessioned2019-11-04T04:04:23Z
dc.date.available2019-11-04T04:04:23Z
dc.date.issued2013
dc.identifier.citationMartín-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
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161290
dc.description.abstractWest 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.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectamino acid
dc.subjectammonium chloride
dc.subjectconcanamycin A
dc.subjectcore protein
dc.subjectglutamine
dc.subjectlysine
dc.subjectvirus protein
dc.subjectacidification
dc.subjectamino acid substitution
dc.subjectanimal experiment
dc.subjectarticle
dc.subjectcontrolled study
dc.subjectendosome
dc.subjectfemale
dc.subjectgenetic stability
dc.subjectmouse
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectpH
dc.subjectphenotype
dc.subjecttrans Golgi network
dc.subjectvirion
dc.subjectvirus entry
dc.subjectvirus envelope
dc.subjectWest Nile flavivirus
dc.subjectAmino Acid Substitution
dc.subjectAmmonium Chloride
dc.subjectAnalysis of Variance
dc.subjectAnimals
dc.subjectBlotting, Western
dc.subjectCercopithecus aethiops
dc.subjectCricetinae
dc.subjectDrug Resistance, Viral
dc.subjectFluorescent Antibody Technique
dc.subjectHydrogen-Ion Concentration
dc.subjectMacrolides
dc.subjectMice
dc.subjectReal-Time Polymerase Chain Reaction
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectVero Cells
dc.subjectViral Core Proteins
dc.subjectVirulence
dc.subjectWest Nile virus
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.pone.0069479
dc.description.sourcetitlePLoS ONE
dc.description.volume8
dc.description.issue7
dc.description.pagee69479
dc.published.statePublished
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