Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0050995
Title: Release of Dengue Virus Genome Induced by a Peptide Inhibitor
Authors: Lok S.-M. 
Costin J.M.
Hrobowski Y.M.
Hoffmann A.R.
Rowe D.K.
Kukkaro P. 
Holdaway H.
Chipman P.
Fontaine K.A.
Holbrook M.R.
Garry R.F.
Kostyuchenko V. 
Wimley W.C.
Isern S.
Rossmann M.G.
Michael S.F.
Keywords: glycoprotein
hemoglobin
protein inhibitor
ribonuclease
RNA
virus protein
article
cryoelectron microscopy
Dengue virus
density gradient
Flavivirus
hemoglobin blood level
incubation time
lipid vesicle
nonhuman
polymerase chain reaction
sensitivity analysis
serotype
virus genome
virus particle
Amino Acid Sequence
Animals
Antiviral Agents
Cell Line
Centrifugation, Density Gradient
Dengue Virus
Genome, Viral
Humans
Lipid Bilayers
Molecular Sequence Data
Peptides
Viral Envelope Proteins
Virion
Dengue virus
Flavivirus
Hexapoda
Mammalia
Issue Date: 2012
Publisher: Public Library of Science
Citation: Lok S.-M., Costin J.M., Hrobowski Y.M., Hoffmann A.R., Rowe D.K., Kukkaro P., Holdaway H., Chipman P., Fontaine K.A., Holbrook M.R., Garry R.F., Kostyuchenko V., Wimley W.C., Isern S., Rossmann M.G., Michael S.F. (2012). Release of Dengue Virus Genome Induced by a Peptide Inhibitor. PLoS ONE 7 (11) : e50995. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0050995
Abstract: Dengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. The mimetic peptide, DN59, consists of residues corresponding to the membrane interacting, amphipathic stem region of the dengue virus envelope (E) glycoprotein. This peptide is inhibitory to all four serotypes of dengue virus, as well as other flaviviruses. Cryo-electron microscopy image reconstruction of dengue virus particles incubated with DN59 showed that the virus particles were largely empty, concurrent with the formation of holes at the five-fold vertices. The release of RNA from the viral particle following incubation with DN59 was confirmed by increased sensitivity of the RNA genome to exogenous RNase and separation of the genome from the E protein in a tartrate density gradient. DN59 interacted strongly with synthetic lipid vesicles and caused membrane disruptions, but was found to be non-toxic to mammalian and insect cells. Thus DN59 inhibits flavivirus infectivity by interacting directly with virus particles resulting in release of the genomic RNA.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/166206
ISSN: 19326203
DOI: 10.1371/journal.pone.0050995
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