Argonaute 2 inhibits RIG-I signaling via competition for viral RNA binding

Interferon (IFN)-dependent responses constitute a critical initial defense against viruses in mammalian cells, while RNA interference (RNAi) acts as an additional strategy to combat invading viral pathogens. Investigating the functionality of mammalian Argonaute 2 (AGO2), an essential component of the RNA-induced silencing complex, we found it to negatively modulate influenza A virus infection-induced RIG-I-mediated antiviral signaling. AGO2 depletion in human cell lines significantly enhanced the RNA virus-triggered phosphorylation of IRF3 and downstream antiviral gene activation. Interestingly, this negative regulation occurred independently of gene silencing via canonical RNA silencing pathways and instead involved the binding of AGO2 to viral RNA molecules carrying 5'-triphosphates or cytosolic RIG-I agonists. These findings highlight AGO2's crucial role in balancing antiviral signaling activation and restricting virus infection to prevent excessive immune responses.

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Publication Details

Journal
iScience
Published
2025-08-20
DOI
https://doi.org/10.1016/j.isci.2025.113391
Citations
1
Primary Topic
interferon and immune responses
Type
article
Field-Weighted Citation Impact
0.80
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article

Argonaute 2 inhibits RIG-I signaling via competition for viral RNA binding

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1 citations
iScience
interferon and immune responses
0.80
article

Argonaute 2 inhibits RIG-I signaling via competition for viral RNA binding

L Li, Conor J. Cremin, Lin Zhu, Guangshan Xie, Honglian Liu, Zongwei Cai, Jiayan Liu, Pui Wang, Wenjun Song, Bobo Wing-Yee Mok, Rachel Chun-Yee Tam, Fei Yu, Shaofeng Deng, Mingyue Zheng, Yixin Chen, Yajie Zhang, Honglin Chen, Siwen Liu, Yajin Liao, Xiaofeng Huang, Kwok-Yung Yuen, Chen Pin
article en
1 citations

Abstract

Interferon (IFN)-dependent responses constitute a critical initial defense against viruses in mammalian cells, while RNA interference (RNAi) acts as an additional strategy to combat invading viral pathogens. Investigating the functionality of mammalian Argonaute 2 (AGO2), an essential component of the RNA-induced silencing complex, we found it to negatively modulate influenza A virus infection-induced RIG-I-mediated antiviral signaling. AGO2 depletion in human cell lines significantly enhanced the RNA virus-triggered phosphorylation of IRF3 and downstream antiviral gene activation. Interestingly, this negative regulation occurred independently of gene silencing via canonical RNA silencing pathways and instead involved the binding of AGO2 to viral RNA molecules carrying 5'-triphosphates or cytosolic RIG-I agonists. These findings highlight AGO2's crucial role in balancing antiviral signaling activation and restricting virus infection to prevent excessive immune responses.

iScienceVol. 28(9)
Hong Kong Baptist University (HK), Xiamen University (CN), Cornell University (US), Shenzhen Bay Laboratory (CN), Shenzhen Baoan High School Group (CN), First Affiliated Hospital Zhejiang University (CN), Weill Cornell Medicine (US), University of Hong Kong (HK)
Openalex Percentile: Top 24%
interferon and immune responses
0.80
DOIOpen Access PDFOpenAlex
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