TY - JOUR
T1 - Influenza virus adaptation PB2-627K modulates nucleocapsid inhibition by the pathogen sensor RIG-I
AU - Weber, Michaela
AU - Sediri, Hanna
AU - Felgenhauer, Ulrike
AU - Binzen, Ina
AU - Bänfer, Sebastian
AU - Jacob, Ralf
AU - Brunotte, Linda
AU - García-Sastre, Adolfo
AU - Schmid-Burgk, Jonathan L.
AU - Schmidt, Tobias
AU - Hornung, Veit
AU - Kochs, Georg
AU - Schwemmle, Martin
AU - Klenk, Hans Dieter
AU - Weber, Friedemann
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/3/11
Y1 - 2015/3/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84926139701&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2015.01.005
DO - 10.1016/j.chom.2015.01.005
M3 - Article
C2 - 25704008
AN - SCOPUS:84926139701
SN - 1931-3128
VL - 17
SP - 309
EP - 319
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -