tetano
Editor, Senior Moderator
Nucleic Acids Res
. 2025 Apr 10;53(7):gkaf268.
doi: 10.1093/nar/gkaf268. Nuclear AGO2 supports influenza A virus replication through type-I interferon regulation
Hsiang-Chi Huang[SUP] 1 2 3 [/SUP], Michelle Fong[SUP] 1 2 [/SUP], Iwona Nowak[SUP] 1 2 [/SUP], Evgeniia Shcherbinina[SUP] 1 2 [/SUP], Vivian Lobo[SUP] 1 2 [/SUP], Danica F Besavilla[SUP] 3 [/SUP], Hang T Huynh[SUP] 1 2 [/SUP], Karin Schön[SUP] 3 [/SUP], Jakub O Westholm[SUP] 4 [/SUP], Carola Fernandez[SUP] 1 2 [/SUP], Angana A H Patel[SUP] 2 5 [/SUP], Clotilde Wiel[SUP] 5 [/SUP], Volkan I Sayin[SUP] 2 5 [/SUP], Dimitrios G Anastasakis[SUP] 6 [/SUP], Davide Angeletti[SUP] 3 7 [/SUP], Aishe A Sarshad[SUP] 1 2 [/SUP]
Affiliations
The role of Argonaute (AGO) proteins and the RNA interference (RNAi) machinery in mammalian antiviral response has been debated. Therefore, we set out to investigate how mammalian RNAi impacts influenza A virus (IAV) infection. We reveal that IAV infection triggers nuclear accumulation of AGO2, which is directly facilitated by p53 activation. Mechanistically, we show that IAV induces nuclear AGO2 targeting of TRIM71and type-I interferon-pathway genes for silencing. Accordingly, Tp53-/- mice do not accumulate nuclear AGO2 and demonstrate decreased susceptibility to IAV infection. Hence, the RNAi machinery is highjacked by the virus to evade the immune system and support viral replication. Furthermore, the FDA-approved drug, arsenic trioxide, prevents p53 nuclear translocation, increases interferon response and decreases viral replication in vitro and in a mouse model in vivo. Our data indicate that targeting the AGO2
53-mediated silencing of innate immunity may offer a promising strategy to mitigate viral infections.
. 2025 Apr 10;53(7):gkaf268.
doi: 10.1093/nar/gkaf268. Nuclear AGO2 supports influenza A virus replication through type-I interferon regulation
Hsiang-Chi Huang[SUP] 1 2 3 [/SUP], Michelle Fong[SUP] 1 2 [/SUP], Iwona Nowak[SUP] 1 2 [/SUP], Evgeniia Shcherbinina[SUP] 1 2 [/SUP], Vivian Lobo[SUP] 1 2 [/SUP], Danica F Besavilla[SUP] 3 [/SUP], Hang T Huynh[SUP] 1 2 [/SUP], Karin Schön[SUP] 3 [/SUP], Jakub O Westholm[SUP] 4 [/SUP], Carola Fernandez[SUP] 1 2 [/SUP], Angana A H Patel[SUP] 2 5 [/SUP], Clotilde Wiel[SUP] 5 [/SUP], Volkan I Sayin[SUP] 2 5 [/SUP], Dimitrios G Anastasakis[SUP] 6 [/SUP], Davide Angeletti[SUP] 3 7 [/SUP], Aishe A Sarshad[SUP] 1 2 [/SUP]
Affiliations
- PMID: 40219968
- PMCID: PMC11992678
- DOI: 10.1093/nar/gkaf268
The role of Argonaute (AGO) proteins and the RNA interference (RNAi) machinery in mammalian antiviral response has been debated. Therefore, we set out to investigate how mammalian RNAi impacts influenza A virus (IAV) infection. We reveal that IAV infection triggers nuclear accumulation of AGO2, which is directly facilitated by p53 activation. Mechanistically, we show that IAV induces nuclear AGO2 targeting of TRIM71and type-I interferon-pathway genes for silencing. Accordingly, Tp53-/- mice do not accumulate nuclear AGO2 and demonstrate decreased susceptibility to IAV infection. Hence, the RNAi machinery is highjacked by the virus to evade the immune system and support viral replication. Furthermore, the FDA-approved drug, arsenic trioxide, prevents p53 nuclear translocation, increases interferon response and decreases viral replication in vitro and in a mouse model in vivo. Our data indicate that targeting the AGO2
53-mediated silencing of innate immunity may offer a promising strategy to mitigate viral infections.