tetano
Editor, Senior Moderator
Cell Host Microbe. 2015 Feb 17. pii: S1931-3128(15)00025-6. doi: 10.1016/j.chom.2015.01.005. [Epub ahead of print]
[h=1]Influenza Virus Adaptation PB2-627K Modulates Nucleocapsid Inhibition by the Pathogen Sensor RIG-I.[/h] Weber M[SUP]1[/SUP], Sediri H[SUP]1[/SUP], Felgenhauer U[SUP]1[/SUP], Binzen I[SUP]1[/SUP], B?nfer S[SUP]2[/SUP], Jacob R[SUP]2[/SUP], Brunotte L[SUP]3[/SUP], Garc?a-Sastre A[SUP]4[/SUP], Schmid-Burgk JL[SUP]5[/SUP], Schmidt T[SUP]5[/SUP], Hornung V[SUP]5[/SUP], Kochs G[SUP]3[/SUP], Schwemmle M[SUP]3[/SUP], Klenk HD[SUP]1[/SUP], Weber F[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2015 Elsevier Inc. All rights reserved.
PMID: 25704008 [PubMed - as supplied by publisher]
[h=1]Influenza Virus Adaptation PB2-627K Modulates Nucleocapsid Inhibition by the Pathogen Sensor RIG-I.[/h] Weber M[SUP]1[/SUP], Sediri H[SUP]1[/SUP], Felgenhauer U[SUP]1[/SUP], Binzen I[SUP]1[/SUP], B?nfer S[SUP]2[/SUP], Jacob R[SUP]2[/SUP], Brunotte L[SUP]3[/SUP], Garc?a-Sastre A[SUP]4[/SUP], Schmid-Burgk JL[SUP]5[/SUP], Schmidt T[SUP]5[/SUP], Hornung V[SUP]5[/SUP], Kochs G[SUP]3[/SUP], Schwemmle M[SUP]3[/SUP], Klenk HD[SUP]1[/SUP], Weber F[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2015 Elsevier Inc. All rights reserved.
PMID: 25704008 [PubMed - as supplied by publisher]