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dc.contributor.authorPérez-Cidoncha, Maite
dc.contributor.authorKillip, Marian J
dc.contributor.authorAsensio, Víctor J
dc.contributor.authorFernández, Yolanda
dc.contributor.authorBengoechea, José A
dc.contributor.authorRandall, Richard E
dc.contributor.authorOrtín, Juan
dc.date.accessioned2014-06-12T12:01:03Z
dc.date.available2014-06-12T12:01:03Z
dc.date.issued2014-06-02
dc.identifier.citationPérez-Cidoncha , M , Killip , M J , Asensio , V J , Fernández , Y , Bengoechea , J A , Randall , R E & Ortín , J 2014 , ' Generation of replication-proficient Influenza Virus NS1 point mutants with interferon-hyperinducer phenotype ' , PLoS One , vol. 9 , no. 6 , e98668 . https://doi.org/10.1371/journal.pone.0098668en
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 127017784
dc.identifier.otherPURE UUID: 6c491027-734b-44f0-9f6b-a468ea2a91f7
dc.identifier.otherPubMed: 24887174
dc.identifier.otherScopus: 84902322320
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60427041
dc.identifier.otherWOS: 000336956300098
dc.identifier.urihttp://hdl.handle.net/10023/4877
dc.description.abstractThe NS1 protein of influenza A viruses is the dedicated viral interferon (IFN)-antagonist. Viruses lacking NS1 protein expression cannot multiply in normal cells but are viable in cells deficient in their ability to produce or respond to IFN. Here we report an unbiased mutagenesis approach to identify positions in the influenza A NS1 protein that modulate the IFN response upon infection. A random library of virus ribonucleoproteins containing circa 40 000 point mutants in NS1 were transferred to infectious virus and amplified in MDCK cells unable to respond to interferon. Viruses that activated the interferon (IFN) response were subsequently selected by their ability to induce expression of green-fluorescent protein (GFP) following infection of A549 cells bearing an IFN promoter-dependent GFP gene. Using this approach we isolated individual mutant viruses that replicate to high titers in IFN-compromised cells but, compared to wild type viruses, induced higher levels of IFN in IFN-competent cells and had a reduced capacity to counteract exogenous IFN. Most of these viruses contained not previously reported NS1 mutations within either the RNA-binding domain, the effector domain or the linker region between them. These results indicate that subtle alterations in NS1 can reduce its effectiveness as an IFN antagonist without affecting the intrinsic capacity of the virus to multiply. The general approach reported here may facilitate the generation of replication-proficient, IFN-inducing virus mutants, that potentially could be developed as attenuated vaccines against a variety of viruses.
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofPLoS Oneen
dc.rights© 2014 Perez-Cidoncha 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.subject.lccQH301en
dc.titleGeneration of replication-proficient Influenza Virus NS1 point mutants with interferon-hyperinducer phenotypeen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0098668
dc.description.statusPeer revieweden


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