Show simple item record

Files in this item


Item metadata

dc.contributor.authorStewart, Claire Emma
dc.contributor.authorRandall, Richard Edward
dc.contributor.authorAdamson, Catherine S
dc.identifier.citationStewart , C E , Randall , R E & Adamson , C S 2014 , ' Inhibitors of the interferon response enhance virus replication in vitro. ' , PLoS One , vol. 9 , no. 11 , e112014 .
dc.identifier.otherPURE: 158007622
dc.identifier.otherPURE UUID: c32e9783-a471-44ea-aa06-020dd43a3588
dc.identifier.otherWOS: 000349144400045
dc.identifier.otherScopus: 84911493910
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60427039
dc.identifier.otherORCID: /0000-0001-7673-5212/work/60630454
dc.descriptionThis work was supported by the University of St Andrews (CSA, CES) and the Wellcome Trust (grant 087751/A/08/Z) (RER).en
dc.description.abstractVirus replication efficiency is influenced by two conflicting factors, kinetics of the cellular interferon (IFN) response and induction of an antiviral state versus speed of virus replication and virus-induced inhibition of the IFN response. Disablement of a virus's capacity to circumvent the IFN response enables both basic research and various practical applications. However, such IFN-sensitive viruses can be difficult to grow to high-titer in cells that produce and respond to IFN. The current default option for growing IFN-sensitive viruses is restricted to a limited selection of cell-lines (e.g. Vero cells) that have lost their ability to produce IFN. This study demonstrates that supplementing tissue-culture medium with an IFN inhibitor provides a simple, effective and flexible approach to increase the growth of IFN-sensitive viruses in a cell-line of choice. We report that IFN inhibitors targeting components of the IFN response (TBK1, IKK2, JAK1) significantly increased virus replication. More specifically, the JAK1/2 inhibitor Ruxolitinib enhances the growth of viruses that are sensitive to IFN due to (i) loss of function of the viral IFN antagonist (due to mutation or species-specific constraints) or (ii) mutations/host cell constraints that slow virus spread such that it can be controlled by the IFN response. This was demonstrated for a variety of viruses, including, viruses with disabled IFN antagonists that represent live-attenuated vaccine candidates (Respiratory Syncytial Virus (RSV), Influenza Virus), traditionally attenuated vaccine strains (Measles, Mumps) and a slow-growing wild-type virus (RSV). In conclusion, supplementing tissue culture-medium with an IFN inhibitor to increase the growth of IFN-sensitive viruses in a cell-line of choice represents an approach, which is broadly applicable to research investigating the importance of the IFN response in controlling virus infections and has utility in a number of practical applications including vaccine and oncolytic virus production, virus diagnostics and techniques to isolate newly emerging viruses.
dc.relation.ispartofPLoS Oneen
dc.rights© 2014. Stewart et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectQH301 Biologyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleInhibitors of the interferon response enhance virus replication in vitro.en
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

This item appears in the following Collection(s)

Show simple item record