Methionine Synthase Positively Regulates Plant Defence to Both <scp>RNA</scp> and <scp>DNA</scp> Viruses and Is Useful for Developing Broad‐Spectrum Antiviral Resistance in Crops

Plant viruses frequently cause severe economic losses in worldwide crop production. Developing broad-spectrum resistance is the most efficient approach for controlling plant viral diseases. In this work, we found that the 17K protein of barley yellow dwarf viruses (BYDVs), which has multiple functions in viral pathogenesis including acting as a viral suppressor of gene silencing (VSR), interacted with plant methionine synthase (MS), the last enzyme in the methionine cycle. Silencing HvMS gene expression enhanced BYDV symptoms and viral gene expression in barley. In contrast, overexpressing HvMS1 in wheat, another important host of BYDVs, attenuated disease symptoms and decreased viral genome proliferation. Interestingly, the γb VSR of barley stripe mosaic virus (BSMV) also interacted with HvMS protein, and HvMS1 overexpression lines likewise exhibited improved BSMV resistance. Further investigations uncovered that the VSRs of potato virus X (PVX) and tobacco rattle virus (TRV) could interact with the MS protein of Nicotiana benthamiana; lowering NbMS gene expression by genome editing reduced tobacco resistance to PVX and TRV, whereas the reverse was observed in HvMS1 overexpression tobacco lines. Finally, we showed that HvMS1 could counteract the VSR function of 10 distinct RNA and DNA viruses by obstructing their ability to revive GFP expression in 16c tobacco, suggesting that plant MS protein may act broadly in disrupting the anti-gene silencing activities of VSRs. Altogether, our data suggest that plant MS protein positively regulates host defence to diverse viruses through inhibiting their VSRs, thus providing a promising target for engineering broad-spectrum antiviral resistance in crops.