Journal article

Publication year: 2015

Pages: 309-319

Journal: Cell Host & Microbe

Volume number: 17

Issue number: 3

ISSN: 1931-3128

eISSN: 1934-6069

DOI Link: https://doi.org/10.1016/j.chom.2015.01.005

Publisher: Cell Press

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.

Harvard Citation style: Weber, M., Sediri, H., Felgenhauer, U., Binzen, I., Bänfer, S., Jacob, R., et al. (2015) Influenza Virus Adaptation PB2-627K Modulates Nucleocapsid Inhibition by the Pathogen Sensor RIG-I, Cell Host & Microbe, 17(3), pp. 309-319. https://doi.org/10.1016/j.chom.2015.01.005

APA Citation style: Weber, M., Sediri, H., Felgenhauer, U., Binzen, I., Bänfer, S., Jacob, R., Brunotte, L., García-Sastre, A., Schmid-Burgk, J., Schmidt, T., Hornung, V., Kochs, G., Schwemmle, M., Klenk, H., & Weber, F. (2015). Influenza Virus Adaptation PB2-627K Modulates Nucleocapsid Inhibition by the Pathogen Sensor RIG-I. Cell Host & Microbe. 17(3), 309-319. https://doi.org/10.1016/j.chom.2015.01.005