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

Michaela Weber, Hanna Sediri, Ulrike Felgenhauer, Ina Binzen, Sebastian Bänfer, Ralf Jacob, Linda Brunotte, Adolfo García-Sastre, Jonathan L. Schmid-Burgk, Tobias Schmidt, Veit Hornung, Georg Kochs, Martin Schwemmle, Hans Dieter Klenk, Friedemann Weber

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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.

Original languageEnglish
Pages (from-to)309-319
Number of pages11
JournalCell Host and Microbe
Volume17
Issue number3
DOIs
StatePublished - 11 Mar 2015

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