Ningnanmycin Activates\nDefense Systems against Potato\nVirus Y in Nicotiana benthamiana

Ningnanmycin has been proven to effectively inhibit infection\nby\npotato virus Y (PVY), although its underlying mechanisms remain unclear.\nIn this study, we report a novel finding that ningnanmycin affects\nPVY replication. Two approaches were employed: studies using PVY movement-deficient\nmutants suggest that ningnanmycin, at a concentration of 500 μg/mL,\ninhibits PVY replication. Ningnanmycin interacts with the PVY-encoded\ncoat protein (CP) with a binding constant of 1.34 μmol/L, and\nkey amino acids Glu<sup>168</sup> and Thr<sup>206</sup> are involved\nin this interaction. Additionally, ningnanmycin induces the expression\nof antiviral response genes in Nicotiana benthamiana, including <i>PRXIIB</i>, <i>PRXIIE</i>, <i>PUB4</i>, and <i>PER42</i>. Furthermore, studies revealed\nthat the overexpression of <i>PUB4</i> in N. benthamiana confers resistance to PVY infection.\nThese findings highlight the mechanisms by which ningnanmycin activates\nthe <i>PUB4</i> gene and suppresses CP assembly, thereby\ninhibiting PVY in N. benthamiana. This\nstudy represents an important step toward elucidating the molecular\nmechanism underlying the antiviral activity of ningnanmycin.