Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions

Swantje Liedmann, Eike R. Hrincius, Cliff Guy, Darisuren Anhlan, Rüdiger Dierkes, Robert Carter, Gang Wu, Peter Staeheli, Douglas R. Green, Thorsten Wolff, Jonathan Mccullers, Stephan Ludwig, Christina Ehrhardt

Research output: Contribution to journalArticle

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Abstract

The type I interferon (IFN) response represents the first line of defence to invading pathogens. Internalized viral ribonucleoproteins (vRNPs) of negative-strand RNA viruses induce an early IFN response by interacting with retinoic acid inducible gene I (RIG-I) and its recruitment to mitochondria. Here we employ three-dimensional stochastic optical reconstruction microscopy (STORM) to visualize incoming influenza A virus (IAV) vRNPs as helical-like structures associated with mitochondria. Unexpectedly, an early IFN induction in response to vRNPs is not detected. A distinct amino-acid motif in the viral polymerases, PB1/PA, suppresses early IFN induction. Mutation of this motif leads to reduced pathogenicity in vivo, whereas restoration increases it. Evolutionary dynamics in these sequences suggest that completion of the motif, combined with viral reassortment can contribute to pandemic risks. In summary, inhibition of the immediate anti-viral response is 'pre-packaged' in IAV in the sequences of vRNP-associated polymerase proteins.

Original languageEnglish (US)
Article number5645
JournalNature communications
Volume5
DOIs
StatePublished - Jan 1 2014

Fingerprint

interferon
influenza
suppressors
Ribonucleoproteins
Tretinoin
genes
Virion
Interferons
Human Influenza
viruses
Genes
Viruses
acids
Mitochondria
mitochondria
Influenza A virus
induction
Interferon Type I
Amino Acid Motifs
pathogens

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Liedmann, S., Hrincius, E. R., Guy, C., Anhlan, D., Dierkes, R., Carter, R., ... Ehrhardt, C. (2014). Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions. Nature communications, 5, [5645]. https://doi.org/10.1038/ncomms6645

Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions. / Liedmann, Swantje; Hrincius, Eike R.; Guy, Cliff; Anhlan, Darisuren; Dierkes, Rüdiger; Carter, Robert; Wu, Gang; Staeheli, Peter; Green, Douglas R.; Wolff, Thorsten; Mccullers, Jonathan; Ludwig, Stephan; Ehrhardt, Christina.

In: Nature communications, Vol. 5, 5645, 01.01.2014.

Research output: Contribution to journalArticle

Liedmann, S, Hrincius, ER, Guy, C, Anhlan, D, Dierkes, R, Carter, R, Wu, G, Staeheli, P, Green, DR, Wolff, T, Mccullers, J, Ludwig, S & Ehrhardt, C 2014, 'Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions', Nature communications, vol. 5, 5645. https://doi.org/10.1038/ncomms6645
Liedmann, Swantje ; Hrincius, Eike R. ; Guy, Cliff ; Anhlan, Darisuren ; Dierkes, Rüdiger ; Carter, Robert ; Wu, Gang ; Staeheli, Peter ; Green, Douglas R. ; Wolff, Thorsten ; Mccullers, Jonathan ; Ludwig, Stephan ; Ehrhardt, Christina. / Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions. In: Nature communications. 2014 ; Vol. 5.
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