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Reference: Meredith, LW, Zitzmann, N and McKeating, JA, (2013). Differential effect of p7 inhibitors on hepatitis C virus cell-to-cell transmission. Antiviral Research, 100 (3), 636-639.Citable link to this page:

 

Differential effect of p7 inhibitors on hepatitis C virus cell-to-cell transmission.

Abstract: Inhibitors targeting the hepatitis C virus (HCV) encoded viroporin, p7 prevent virus release in vitro. HCV can transmit by cell-free particle infection of new target cells and via cell-to-cell dependent contact with limited exposure to the extracellular environment. The role of assembly inhibitors in preventing HCV transmission via these pathways has not been studied. We compared the efficacy of three published p7 inhibitors to inhibit cell-free and cell-to-cell transmission of two chimeric HCV strains encoding genotype 2 (GT2) or 5 (GT5) p7 using a recently developed single cycle co-culture assay. The inhibitors reduced the infectivity of extracellular GT2 and GT5 virus by 80-90% and GT2 virus cell-to-cell transmission by 50%. However, all of the p7 inhibitors had minimal effect on GT5 cell contact dependent transmission. Screening a wider panel of diverse viral genotypes demonstrated that p7 viroporin inhibitors were significantly more effective at blocking cell-free virus than cell-to-cell transmission. These results suggest an altered assembly or trafficking of cell-to-cell transmitted compared to secreted virus. These observations have important implications for the validation, therapeutic design and testing of HCV assembly inhibitors.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Medical Research Council   Funder: NIHR Centre for Liver Research   Funder: Wellcome Trust   Notes:© 2013 The Authors. Published by Elsevier B.V. All rights reserved. This is the publisher's version of the article. The final version is available online from Elsevier at: [10.1016/j.antiviral.2013.10.006].

Bibliographic Details

Publisher: Elsevier

Publisher Website: http://www.elsevier.com

Journal: Antiviral Researchsee more from them

Publication Website: http://www.journals.elsevier.com/antiviral-research

Issue Date: 2013-10-21

pages:636-639Identifiers

Urn: uuid:225970a2-a386-4cb3-af13-fa90ba1cc133

Source identifier: 436103

Eissn: 1872-9096

Doi: https://doi.org/10.1016/j.antiviral.2013.10.006

Issn: 0166-3542 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Cell Line Humans Hepacivirus Reassortant Viruses Guanidines Rimantadine 1-Deoxynojirimycin Pyrazoles Viral Proteins Antiviral Agents Coculture Techniques Virus Cultivation Virus Assembly Cell Communication Genotype Virus Attachment Tiny URL: pubs:436103

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Autor: Meredith, LW - - - Zitzmann, N - institutionUniversity of Oxford Oxford, MSD, Biochemistry - - - McKeating, JA - - - - Bibliograp

Fuente: https://ora.ox.ac.uk/objects/uuid:225970a2-a386-4cb3-af13-fa90ba1cc133



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