Format

Send to

Choose Destination
Cell Host Microbe. 2015 Mar 11;17(3):309-319. doi: 10.1016/j.chom.2015.01.005. Epub 2015 Feb 19.

Influenza virus adaptation PB2-627K modulates nucleocapsid inhibition by the pathogen sensor RIG-I.

Author information

1
Institute for Virology, Philipps-University Marburg, D-35043 Marburg, Germany.
2
Department of Cell Biology and Cell Pathology, Philipps-University Marburg, D-35043 Marburg, Germany.
3
Institute for Virology, University Medical Center, D-79008 Freiburg, Germany.
4
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Institute of Molecular Medicine, University Hospital, University of Bonn, D-53127 Bonn, Germany.
6
Institute for Virology, Philipps-University Marburg, D-35043 Marburg, Germany. Electronic address: friedemann.weber@staff.uni-marburg.de.

Abstract

The cytoplasmic RNA helicase RIG-I mediates innate sensing of RNA viruses. The genomes of influenza A virus (FLUAV) are encapsidated by the nucleoprotein and associated with RNA polymerase, posing potential barriers to RIG-I sensing. We show that RIG-I recognizes the 5'-triphosphorylated dsRNA on FLUAV nucleocapsids but that polymorphisms at position 627 of the viral polymerase subunit PB2 modulate RIG-I sensing. Compared to mammalian-adapted PB2-627K, avian FLUAV nucleocapsids possessing PB2-627E are prone to increased RIG-I recognition, and RIG-I-deficiency partially restores PB2-627E virus infection of mammalian cells. Heightened RIG-I sensing of PB2-627E nucleocapsids correlates with previously established lower affinity of 627E-containing PB2 for nucleoprotein and is increased by further nucleocapsid instability. The effect of RIG-I on PB2-627E nucleocapsids is independent of antiviral signaling, suggesting that RIG-I-nucleocapsid binding alone can inhibit infection. These results indicate that RIG-I is a direct avian FLUAV restriction factor and highlight nucleocapsid disruption as an antiviral strategy.

Comment in

PMID:
25704008
PMCID:
PMC4359673
DOI:
10.1016/j.chom.2015.01.005
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center