Significance In plants, RNA interference (RNAi) is the main antiviral defense mechanism. RNAi moves cell-to-cell through cytoplasmic channels called plasmodesmata, spreading ahead of the viral infection to immunize tissues before arrival of the virus. How this movement is regulated has been elusive. Here, we identify a plant protein, BAM1, localized at plasmodesmata and promoting RNAi spread; both BAM1 and its closest homolog, BAM2, are required for this process. In agreement with their role in promoting RNAi movement, we found that BAM1 and BAM2 are targeted by a viral effector, which acts as a suppressor of RNAi spread. Our work offers insight into the regulation of cell-to-cell spread of RNAi and provides another example of the arms race between pathogens and hosts.