Format

Send to

Choose Destination
Nat Commun. 2014 Dec 9;5:5645. doi: 10.1038/ncomms6645.

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

Author information

1
Institute of Molecular Virology (IMV), Center for Molecular Biology of Inflammation (ZMBE), University of Muenster, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
2
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
3
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
4
Department of Computational Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
5
Institute of Virology, University Medical Center Freiburg, Hermann-Herder-Street 11, D-79104 Freiburg, Germany.
6
Division of Influenza and Other Respiratory Viruses, Seestraβe 10, Robert Koch-Institut, D-13353 Berlin, Germany.
7
1] Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA [2] Department of Pediatrics, University of Tennessee Health Sciences Center, 50 N. Dunlap, Memphis, Tennessee 38103, USA.
8
1] Institute of Molecular Virology (IMV), Center for Molecular Biology of Inflammation (ZMBE), University of Muenster, Von-Esmarch-Street 56, D-48149 Muenster, Germany [2] Cluster of Excellence Cells in Motion, University of Muenster, Muenster, Germany.

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.

PMID:
25487526
PMCID:
PMC4268707
DOI:
10.1038/ncomms6645
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center