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dc.contributor.authorte Velthuis, Aartjan J.W.
dc.contributor.authorLong, Joshua C.
dc.contributor.authorBauer, David L.V.
dc.contributor.authorFan, Rebecca L.Y.
dc.contributor.authorYen, Hui Ling
dc.contributor.authorSharps, Jane
dc.contributor.authorSiegers, Jurre Y.
dc.contributor.authorKillip, Marian J.
dc.contributor.authorFrench, Hollie
dc.contributor.authorOliva-Martín, Maria José
dc.contributor.authorRandall, Richard E.
dc.contributor.authorde Wit, Emmie
dc.contributor.authorvan Riel, Debby
dc.contributor.authorPoon, Leo L.M.
dc.contributor.authorFodor, Ervin
dc.identifier.citationte Velthuis , A J W , Long , J C , Bauer , D L V , Fan , R L Y , Yen , H L , Sharps , J , Siegers , J Y , Killip , M J , French , H , Oliva-Martín , M J , Randall , R E , de Wit , E , van Riel , D , Poon , L L M & Fodor , E 2018 , ' Mini viral RNAs act as innate immune agonists during influenza virus infection ' , Nature Microbiology , vol. 3 , pp. 1234–1242 .
dc.identifier.otherPURE: 256174540
dc.identifier.otherPURE UUID: 062a7e72-9777-4ea6-acc3-d32304cd47a4
dc.identifier.otherScopus: 85053552716
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60426994
dc.identifier.otherWOS: 000448229100010
dc.descriptionWe thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant 090532/Z/09/Z) for the generation of adapter-ligated mvRNA sequencing data. This work was supported by the Wellcome Trust grant 098721/Z/12/Z, the joint Wellcome Trust and Royal Society grant 206579/Z/17/Z and a Netherlands Organization for Scientific Research (NWO) grant 825.11.029 to A.J.W.t.V.; EPA Cephalosporin Junior Research Fellowship to D.L.V.B.; support by the Intramural Research Program of NIAID, NIH, to E.d.W.; Research Grants Council of the Hong Kong Special Administrative Region, China, project no. T11-705/14N and a Croucher Senior Research Fellowship to L.L.M.P.; and Medical Research Council (MRC) programme grants MR/K000241/1 and MR/R009945/1 to E.F. and studentship to J.C.L.en
dc.description.abstractThe molecular processes that determine the outcome of influenza virus infection in humans are multifactorial and involve a complex interplay between host, viral and bacterial factors1. However, it is generally accepted that a strong innate immune dysregulation known as ‘cytokine storm’ contributes to the pathology of infections with the 1918 H1N1 pandemic or the highly pathogenic avian influenza viruses of the H5N1 subtype2,3,4. The RNA sensor retinoic acid-inducible gene I (RIG-I) plays an important role in sensing viral infection and initiating a signalling cascade that leads to interferon expression5. Here, we show that short aberrant RNAs (mini viral RNAs (mvRNAs)), produced by the viral RNA polymerase during the replication of the viral RNA genome, bind to and activate RIG-I and lead to the expression of interferon-β. We find that erroneous polymerase activity, dysregulation of viral RNA replication or the presence of avian-specific amino acids underlie mvRNA generation and cytokine expression in mammalian cells. By deep sequencing RNA samples from the lungs of ferrets infected with influenza viruses, we show that mvRNAs are generated during infection in vivo. We propose that mvRNAs act as the main agonists of RIG-I during influenza virus infection.
dc.relation.ispartofNature Microbiologyen
dc.rights©2020 Macmillan Publishers Limited. All Rights Reserved. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at
dc.subjectQR180 Immunologyen
dc.subjectCell Biologyen
dc.subjectApplied Microbiology and Biotechnologyen
dc.subjectMicrobiology (medical)en
dc.titleMini viral RNAs act as innate immune agonists during influenza virus infectionen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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