A mutually antagonistic mechanism mediated by RNA m6A modification in plant-virus interactions

RNA-based immunity plays a central role in host defense against pathogens, with both hosts and pathogens continually evolving antagonistic strategies in their ongoing arms race. Although the presence of N6-methyl-adenosine (m6A) in viruses has been recognized for decades, its functional significance in plant antiviral defenses has only recently been revealed. Moreover, viral counterstrategies targeting m6A-mediated defenses remain largely unexplored. Here, we uncover a mutually antagonistic mechanism between m6A-mediated antiviral defense and a countermeasure employed by the RNA virus Cucumber mosaic virus (CMV). The deposition of m6A modification on CMV genomic RNAs was validated through m6A antibody-mediated MeRIP and nanopore-based direct RNA sequencing (DRS). During infection, plant m6A methyltransferases are translocated to the cytoplasm through their interaction with the viral coat protein (CP), facilitating viral m6A deposition. The plant EVOLUTIONARILY CONSERVED C-TERMINAL REGION 8 (ECT8) protein acts as a reader of viral m6A, destabilizing viral RNAs and mediating antiviral activity. Conversely, the CMV-2b protein, known as a viral suppressor of RNA silencing (VSR), antagonizes this defense by inhibiting viral m6A deposition. This occurs via direct interactions between 2b and the m6A methyltransferase components MTB and HAKAI, disrupting the methyltransferase complex’s functionality. Furthermore, CMV-2b also downregulates global plant m6A levels, leading to the misexpression of defense-related transcripts. Collectively, our findings elucidate a previously unrecognized layer of host-virus interaction in which m6A modification serves as a regulatory battleground, positioning m6A dynamics as a new frontier in plant-virus coevolution. Liu et al. reveal that m6A RNA modification enhances plant antiviral defense against Cucumber mosaic virus, while the virus counters by suppressing m6A deposition, highlighting a molecular battleground in plant–virus interaction.