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Cleavage of Bcl-2-associated athanogene by metacaspase determines plant antiviral immunity

Lin Liang, Yuhang Jiang, Pingzhi Zhao, Hongwei Wang, Xiaoyue Chen, Xiao Lin, Yanwei Sun, Wenqian Zhang, Rongxiang Fang and Jian Ye ()
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Lin Liang: Chinese Academy of Sciences
Yuhang Jiang: Chinese Academy of Sciences
Pingzhi Zhao: Chinese Academy of Sciences
Hongwei Wang: Chinese Academy of Sciences
Xiaoyue Chen: Chinese Academy of Sciences
Xiao Lin: Chinese Academy of Sciences
Yanwei Sun: Chinese Academy of Sciences
Wenqian Zhang: Chinese Academy of Sciences
Rongxiang Fang: Chinese Academy of Sciences
Jian Ye: Chinese Academy of Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Nucleotide-binding leucine-rich repeat receptors (NLRs) function as core components of innate immunity in both plants and animals. In animals, NLR activation initiates caspase-mediated immune signaling. In contrast, plants lack caspases but instead contain metacaspases (MCAs/MCs), yet their role in antiviral immunity and whether they interface with NLR signaling remain largely unexplored. Here, we demonstrate that cleavage of the conserved immune regulator Bcl-2-associated athanogene 3 (BAG3) by metacaspase 4 (MCAIIa/MC4) induces cell death and activates antiviral immunity in plants. Upon Begomovirus infection, MC4 cleaves BAG3 to release its N-terminal functional domain (BAG3-N) from autoinhibition. BAG3-N assembles into oligomers and induces cell death, effectively inhibiting viral replication. This signaling also interfaces with NLR networks in certain plant species. Viral replication-associated proteins (Reps) counteract this defense response by binding to BAG3-N, highlighting an evolutionary arms race between plants and viruses. Evolutionary analyses reveal that a lysine substitution at position 50 of BAG3 confers its ability to induce cell death in angiosperms. These findings identify BAG3 as a conserved immune regulator linking metacaspase activation to antiviral defense, providing a mechanistic basis for engineering crops with enhanced resistance to insect-borne viruses.

Date: 2025
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DOI: 10.1038/s41467-025-64021-w

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