A viral protein promotes host L-asparaginase activity and weakens the asparagine-induced resistance pathway for the benefit of virus infection

Amino acids are not only essential for plant nutrition but also serve as critical immune signaling molecules, particularly during pathogen invasion. Pathogens can manipulate amino acid metabolic pathways to counteract host immune defenses, yet the underlying mechanisms remain poorly understood. Here, we demonstrate that the Pepper mild mottle virus (PMMoV) 126 kDa protein interacts with host L-asparaginase (LA), identified as a negative regulator of antiviral defense. LA converts asparagine (Asn) to aspartic acid (Asp). Exogenous application of Asn markedly enhanced resistance to PMMoV, whereas Asp produced the opposite effect. Transcriptomic analysis revealed that Asn activates key antiviral immune pathways involving salicylic acid (SA), ethylene (Eth), and reactive oxygen species (ROS), while Asp suppresses them. Further experiments showed that the 126 kDa protein binds directly to the LA active region, enhancing its enzymatic activity and promoting Asn-to-Asp conversion, thereby weakening immune signaling. This process may also involve the VSR (viral suppressor of RNA silencing) function of the 126 kDa protein. Notably, LA also interacts with pathogenic proteins from other RNA viruses (e.g., CMV 2b, RSV NS3, TBSV P19) and facilitates Tomato bush stunt virus (TBSV) accumulation. This study elucidates how viruses exploit amino acid metabolism to promote infection and provides a novel strategy for environmentally friendly control of pepper viral diseases.