A key heavy metal-binding protein orchestrates plant resistance against a geminivirus

Heavy metal-binding proteins (HMPs) are crucial for heavy metal ion transportation in plants, which is involved in plant nutrient absorption, morphogenesis, and immune responses. However, the molecular mechanism enabling the role of HMPs in plant defense in the presence of heavy metal ions has so far remained elusive. Here we show that NbHMP04 mediates host defenses against the geminivirus tomato yellow leaf curl China virus (TYLCCNV) by enhancing the stability of NbNPR1, and that this action is countered by a viral effector. NbHMP04-dependent host defenses against TYLCCNV are activated in the presence of copper ions, which enhances the interaction between NbHMP04 and NbNPR1, increasing NbNPR1 stability and up-regulating downstream gene expression. The TYLCCNB-encoded βC1 protein, however, interacts with NbHMP04 and induces NbHMP04 autophagic degradation to interrupt host immune responses. The TYLCCNV/TYLCCNB (βC1^Y110A) mutant virus caused milder disease symptoms in the infected Nicotiana benthamiana plants. These findings provide novel insights into the mechanism by which copper enhances plant defense and reveal how geminiviruses have evolved to counter these defense responses during infection.