Repository logo
 
Publication

Nucleozin Targets Cytoplasmic Trafficking of Viral Ribonucleoprotein-Rab11 Complexes in Influenza A Virus Infection

2013Journal article Open access
Simple item page
dc.contributor.authorAmorim, M. J.
dc.contributor.authorKao, R. Y.
dc.contributor.authorDigard, P.
dc.date.accessioned2015-10-21T14:31:03Z
dc.date.available2015-10-21T14:31:03Z
dc.date.issued2013
dc.description.abstractNovel antivirals are needed to supplement existing control strategies for influenza A virus (IAV). A promising new class of drug, exemplified by the compound nucleozin, has recently been identified that targets the viral nucleoprotein (NP). These inhibitors are thought to act as "molecular staples" that stabilize interactions between NP monomers, promoting the formation of nonfunctional aggregates. Here we detail the inhibitory mechanism of nucleozin, finding that the drug has both early- and late-acting effects on the IAV life cycle. When present at the start of infection, it inhibited viral RNA and protein synthesis. However, when added at later time points, it still potently blocked the production of infectious progeny but without affecting viral macromolecular synthesis. Instead, nucleozin blocked the cytoplasmic trafficking of ribonucleoproteins (RNPs) that had undergone nuclear export, promoting the formation of large perinuclear aggregates of RNPs along with cellular Rab11. This effect led to the production of much reduced amounts of often markedly smaller virus particles. We conclude that the primary target of nucleozin is the viral RNP, not NP, and this work also provides proof of the principle that IAV replication can be effectively inhibited by blocking cytoplasmic trafficking of the viral genome.pt_PT
dc.description.sponsorshipMRC grant: (G0700815), University of Cambridge/Trinity College grant: (Newton Trust), RGC Hong Kong grant: (GRF 768010 M).pt_PT
dc.identifier10.1128/JVI.03123-12
dc.identifier.citationNucleozin Targets Cytoplasmic Trafficking of Viral Ribonucleoprotein-Rab11 Complexes in Influenza A Virus Infection Maria Joao Amorim, Richard Y. Kao, and Paul Digard J. Virol. April 2013 87:8 4694-4703; Accepted manuscript posted online 13 February 2013, doi:10.1128/JVI.03123-12pt_PT
dc.identifier.doi10.1128/JVI.03123-12
dc.identifier.urihttp://hdl.handle.net/10400.7/423
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Microbiologypt_PT
dc.relation.publisherversionhttp://jvi.asm.org/content/87/8/4694.longpt_PT
dc.subjectRibonucleoproteinspt_PT
dc.subjectInfluenza A viruspt_PT
dc.subjectInfectionpt_PT
dc.titleNucleozin Targets Cytoplasmic Trafficking of Viral Ribonucleoprotein-Rab11 Complexes in Influenza A Virus Infectionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage4703pt_PT
oaire.citation.issue8pt_PT
oaire.citation.startPage4694pt_PT
oaire.citation.titleJournal of Virologypt_PT
oaire.citation.volume87pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
J. Virol.-2013-Amorim-4694-703.pdf
Size:
3.54 MB
Format:
Adobe Portable Document Format
Description:
artigo principal
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

CBVI- Artigos